Pharmaceutical Engineering

Materials Of Plant Construction

Several pieces of equipment are used in the pharmaceutical industry made up of different materials. The processing of the pharmaceutical industry involves the use of many types of chemicals that can destroy the construction material. Further. some processes involve high pressure, temperature etc. so the selection of materials for plant construction becomes very important to run the industry effectively.

Factors Influencing the Selection of Materials of Construction:

The selection of a material for the construction of equipment depends on the following properties:

1. Chemical factors
   • Contamination of the product
   • Corrosion of material of construction
2. Physical factors
   • Strength
   • Wear properties
   • Thermal expansion
   • Cleaning
   • Mass
   • Thermal conductivity
   • Ease of fabrication
   • Sterilization
   • Transparency
3. Economic factors

1. Chemical factors:

During the processing, every time a chemical substance or drug comes in direct contact with the equipment. Therefore, the product can get contaminated with the construction material or the construction material may get destroyed due to such direct contact (we can be called it corrosion).

1. Contamination of product: Contamination of product due to construction material may result in a change in color of the product or there may be an occurrence of degradation of product due to chemical reaction. Leeching of glass may make aqueous products alkaline. This alkaline medium will be hazardous to the products which are unstable in alkaline medium. Heavy metals such as lead inactivate penicillin.
2. Corrosion of material of construction: The products may be corrosive in nature. They may react with the material of construction and destroy it. The life of the equipment is reduced. Extreme pH, strong acids, strong alkalies, powerful oxidizing agents, tannins etc react with the materials, hence some alloys having special chemical resistance are used.

2. Physical factors:

• Strength: Many processes in pharmaceutical industries involve extreme pressure or stressed conditions.
  • So the material must have sufficient physical strength to withstand the required pressure and stresses.
  • Iron and steel can satisfy these properties. Tablet punching machine, die, upper and lower punch sets are made of stainless steel to withstand the very high pressure.
  • Aerosol containers must withstand very high pressure, so tin plate container coated with some polymers are used.
  • Plastic materials are weak so they are used in some packaging materials, like blister packs.
• Mass: For transportation lightweight packaging materials are used. Plastic, aluminum, and paper packaging materials are used for packing pharmaceutical products.
• Wear properties: When there is a possibility of friction between two surfaces, the softer surface wears off and these materials contaminate the products. For example, during milling and grinding the grinding surfaces may wear off and contaminate the powder. When a pharmaceutical product of very high purity is required ceramic and iron grinding surfaces are not used.
• Thermal conductivity: In evaporators, dryers, stills, and heat exchangers the materials employed have very good thermal conductivity. In this case, iron, copper, or graphite tubes are used for effective heat transfer.
• Thermal expansion: If the material has a very high thermal expansion coefficient then as temperature increases the shape of the equipment changes. This produces uneven stresses and may cause fractures. So such materials should be used that can maintain the shape and dimension of the equipment at the working temperature.
• Ease of fabrication: During the fabrication of equipment, the materials undergo various processes such as casting, welding, forging mechanization, etc.
  • For example: Glass and plastic may be easily molded into containers of different shapes and sizes. Glass can be used as lining material for reaction vessels.
• Cleaning: Smooth and polished surfaces make cleaning easy. After an operation is complete, the equipment is cleaned thoroughly so the previous product cannot contaminate the next product. Glass and stainless steel surfaces can be smooth and polished and, hence are easy to clean.
• Sterilization: In the production of parenteral, ophthalmic, and bulk drug products all the equipment is required to be sterilized. This is generally done by introducing steam under high pressure. The material must withstand this high temperature (121°C) and pressure (15 pounds per square inch). If rubber materials are there it should be vulcanized to withstand the high temperature.
• Transparency: In reactors and fermentors, a visual port is provided to observe the progress of the process going on inside the chamber. In this case, borosilicate glass is often used.

In parenteral and ophthalmic containers the particles, if any, are observed from with polarized light. The walls of the containers must be transparent to see through it. Here also glass is the preferred material.

3. Economic factors:

The initial cost of the equipment depends on the material used. Several materials may be suitable for construction from physical and chemical points of view, but from all the materials only the cheapest material is chosen for the construction of the equipment.

Materials that require lower maintenance cost are used because in long run it is economical.

Materials used for Plant Construction Classification

• Metals:
  • Ferrous metals – Cast.iron, stainless steel, steel carbon.
  • Non-ferrous- Aluminium, lead.
• Non-metals:
  • Inorganic- Glass.
  • Organic- Rubber, plastics..

1. Ferrous metals:

1. Cast Iron:

This iron consists of carbon of more than 1.5%. A different proportion of carbon confers different properties to the steel.

Cast Iron Properties:

• Cast iron is resistant to concentrated sulfuric acid, nitric acid and dilute alkalis.
• Cast iron is attacked by dilute sulfuric acid, dilute nitric acid and dilute and concentrated hydrochloric acid.
• Cast iron has low thermal conductivity.
• It is not corrosion resistant hence it is alloyed with Silicon, Nickel or Chromium to produce corrosion resistance.
• It is brittle so it is tough to machine.

Cast Iron Applications:

• It is used as support for plants.
• Thermal conductivity is low hence used as the outer wall of the steam jacket.
• It is cheap and hence used in place of more expensive materials by coating with enamel or plastic.

2. Carbon Steel or Mild Steel:

Mild steel (or carbon steel) is an iron alloy that contains a small percentage of carbon (less than 1.5%).

Carbon Steel or Mild Steel Properties:

• It has greater mechanical strength than cast iron.
• It is easily weldable.
• Has limited corrosion resistance. This property can be increased by proper alloying.
• It reacts with caustic soda, and brine (concentrated NaCI solution).

Carbon Steel or Mild Steel Applications:

• Used for the construction of bars, pipes, and plates.
• Used to fabricate large storage tanks for water, sulfuric acid, organic solvents etc.
• Used as the supporting structure of grinders and bases of vessels.

3. Stainless Steel:

Stainless steel is an alloy of iron usually of nickel and chromium. For pharmaceutical use stainless steel contains 18% chromium and 8% nickel. This steel is called 18/8 stainless steel.

Stainless Steel Properties:

• It is heat resistant.
• Corrosion resistant.
• Ease of fabrication.
• Cleaning and sterilization is easy.
• Has good tensile strength.
• During heat welding the corrosion resistant properties of stainless steel may be reduced due to deposition of carbide precipitate at the crystal grain boundaries.
• This steel is stabilized by the addition of minor quantities of titanium, molybdenum or niobium.

Stainless Steel Applications:

• Storage and extraction vessels, evaporators, and fermenting vessels.
• Small apparatus like funnels, buckets, and measuring vessels.
• Sinks and bench tops.
• In penicillin production plants nearly all equipment is made of stainless steel.

2. Non-ferrous metals:

Aluminium:

Aluminum Properties:

• Pure aluminium is softer and more corrosion-resistant than its alloys. Small percentages of manganese, magnesium, or silicon produce strong, corrosion resistant aluminum alloys  –  Duralumin
• It is attacked by mineral acids, alkali, mercury and its salts.
• It is resistant to strong nitric acid.
• It is resistant to acetic acid due to the formation of a gelatinous surface film of aluminum subacetate.
• Low density hence lighter.

Aluminum Applications:

• The salts of aluminum are colorless and non-toxic to micro-organisms, hence used for fermenting vessels for the biosynthetic production of citric acid, gluconic acids and streptomycin.
• Used for making extraction and absorption vessels in preparation of antibiotics.
• Storage vessels of acetic acid and ammonia.
• Plants for nitric acid is used.
• Because of its lightness large containers such as drums, barrels, and road and rail tankers are made with aluminum.

3. Inorganic non-metals

Glass Preparation:

• Glass is composed principally of sand (Silica – SiO₂), Soda-ash (Na₂CO₃ – Sodium carbonate), and limestone (CaCO₃ – Calcium carbonate).
• Glass made from pure silica consists of a three-dimensional network of silicon atoms each of which is surrounded by four oxygen atoms and in this way, the tetrahedra are linked together to produce the network.

Glass prepared from pure silica requires a very high temperature to fuse, hence ash and lime is used to reduce the melting point.

1. Glass made of pure silica has a network: Properties:

• It is very hard.
• It is chemically resistant.
• The melting point is very high so it is very difficult to mould.

2. Glass made of pure silica + NaO₂: Properties:

• The structure is less rigid so low melting point and is easier to mold.
• The glass is too rapidly attacked by water and NaOH is leached out of the glass.

3. Pure silica + CaO (or BaO, MgO, PbO and ZnO): Properties:

• Divalent oxides do not break the network of pure silica but only push the tetrahedron apart. It is more rigid than the soda-silica network.
• Since the bond is stronger, hence chemical reactivity is lowered.

4. Pure silica + Boric (B₂O₃) or Aluminium oxide (Al₂O₃):

• Since boric oxide is acidic, it does not disrupt the network of silica but forms tetrahedron itself; however, these tetrahedrons are not of the same size as silicon tetrahedra.
• Therefore, the lattice becomes distorted, and this produces flexibility.
• It is chemically resistant.

Glass Container Advantages:

• They are quite strong and rigid.
• They are transparent which allows the visual inspection of the contents; especially in ampoules and vials.
• They are available in various shapes and sizes. Visually elegant containers attract the patients.
• Borosilicate (Type-1) and Neutral glasses are resistant to heat so they can be readily sterilized by heat.
• Glass containers can be easily cleaned without any damage to its surface
  • For example: Scratching or bruising.
• Borosilicate type of glass is chemically inert. Treated soda lime glass has a chemically inert surface.
• As the composition of glass may be varied by changing the ratio of various glass constituents the proper container according to desired qualities can be produced.
• They do not deteriorate with age if provided with proper closures.
• Photosensitive drugs may be saved from UV rays by using amber color glass.
• They are cheaper than other packaging materials.

Glass Container Disadvantages:

• They are brittle and break easily.
• They may crack when subject to sudden changes in temperatures.
• They are heavier in comparison to plastic containers.
• Transparent glasses give passage to UV light which may damage the photosensitive drugs inside the container.
• Flaking: From simple soda-lime glass the alkali is extracted from the surface of the container and a silicate-rich layer is formed which sometimes gets detached from the surface and can be seen in the contents in the form of shining plates – known as ‘flakes’ and in the form of needles – they are known as ‘spicules’. This is a serious problem, especially in parenteral preparations.
• Weathering: Sometimes moisture is condensed on the surface of a glass container which can extract some weakly bound alkali leaving behind a white deposit of alkali carbonate to remain over there, further condensation of moisture will lead to the formation of an alkaline solution which will dissolve some silica resulting in loss of brilliance from the surface of glass – called weathering.

To prevent weathering, the deposited white layer of alkali carbonates should be removed as early as possible by washing the containers with a dilute solution of acid and then washing them thoroughly with water.

5. Lead:

It is used to make collapsible tubes for topically applied products. It is very cheap. In pharmaceutical industries, its use is very limited due to its toxic nature.

Lead Disadvantage:

It has a low melting point and hence possesses poor structural qualities.

6. Copper:

• Copper is malleable and ductile. It has eight times more thermal conductivity than steel. It is attacked by nitric acid in all concentrations, by hot concentrated HCl and H₂SO₄.
• It is used in pharmaceutical industries after tin coating. It is used for heating pans, evaporators, and stills. It is more prone to corrosion.
• Other non-ferrous metals are silver, nickel, chromium, etc.

4.  Inorganic nonmetal

1. Plastic:

Plastics can be categorized as:

• Rigid material
• Flexible material
• Coatings and linings
• Cement and filters

Keebush is an example of a rigid material. It is a phenolic resin with various inert fillers. It can be machined, welded, and worked and is resistant. It can be used for gears, bearings, and similar items with a noise reduction compared to iron. Its weight is about 2/4th that of iron.

It is resistant to corrosion except oxidizing substances and strong alkalis, pipes, fittings, valves, pumps, fans, ducts and made using this material.

• Polyethylene is the cheapest plastic. It is unaffected by most solvents, strong acids; and alkalies.
• Its density ranges from 0.91 to 0.96 determines its stiffness, moisture vapor, transmission, stress cracking, and translucency.
• The stiffness and stress resistance increase with density and permeability to gases decreases.
• Polypropylene has similar chemical resistance as polyethylene but it can be used at higher temperatures. Hot aromatic and halogenated solvents soften it.
• Unplasticized polyvinyl chloride is very clear, tough, and inert but tends to crack readily.
• Plasticizers are added to overcome this weakness. Stabilizers, antioxidants and lubricants may also be added.

2. Rubber:

These are widely used as lining materials. Several synthetic rubbers have been developed, while none has all the properties of natural rubber, they are superior in one or more ways.

• The isoprene and polybutadiene rubbers are duplicates of natural ones. Natural rubber is resistant to dilute mineral acids, alkalies, and salts, but oxidizing media, oils, benzene and ketones attack it Hard and soft rubbers are frequently used for handling acids especially dilute aqueous solutions.
• They cannot resist oxidizing agents and are swelled by organic solvents. Soft rubber is used as a lining for steel while hard rubber is used alone: Hard rubber is made by adding 25% or more of sulphur to natural or synthetic rubber and as such is hard and strong.
• Synthetic rubbers are becoming of increasing importance due to their superiority to natural rubber in many properties such as resistance to oxidation, solvents, oils, and many chemicals.
• Neoprene rubber is resistant to attack, by sunlight, oils, aromatic or halogenated solvents. Styrene rubber has chemical resistance similar to natural. Nitrile rubber is known fat resistance to oils and solvents.

Corrosion

Corrosion is a natural process, which converts a metal to a more chemically-stable form, such as its oxide, hydroxide, or sulfide.

It is the gradual destruction of materials (usually metals) by chemical and/or electrochemical reactions with their environment.

• Corrosion can be defined as the reaction of metallic material with its environment, which causes undesirable changes in the material and can result in a functional failure of the metal.
• Corrosion can also occur in materials other than metals, such as ceramics or polymers. Corrosion degrades the useful properties of materials and structures including strength, appearance, and permeability to liquids and gases.
• Corrosion can be concentrated locally to form a pit or crack, or it can extend across a wide area, corroding the surface. Because corrosion is a diffusion-controlled process, it occurs on exposed surfaces.
• As a result, methods to reduce the activity of the exposed surface, such as passivation and chromate conversion, can increase a material’s corrosion resistance.

Corrosion Theories 

The metal surface undergoes an electrochemical reaction with the moisture and oxygen in the atmosphere. This- theory is called as electrochemical theory of corrosion. The mechanism involves the formation of galvanic cells (anodic and cathodic areas), by different metals or in different areas on the same piece of metal. When galvanic cells are formed on different metals, the corrosion is known as galvanic corrosion.

1. Corrosion reaction on single metal:

A single piece of metal (Fe) when comes in contact with acid (HCI ) small galvanic cells may be set up on the surface. Each galvanic cell consists of anode regions and cathode regions.

Reaction at anode:

Fe on the iron leaves two electrons in the metal and itself becomes Fe⁺⁺ ion. Fe⁺⁺ ion is soluble in water, so it is released in the medium. Thus the iron surface is corroded.

Reaction at the cathode:

The released electron is conducted through the metal piece into the cathode region. Two electrons are supplied to two protons (H⁺) to form two atoms of H. Hydrogen atoms are unstable, hence two H atoms will combine to form a molecule of stable H_². In the absence of acid, water itself dissociates to generate H⁺ Ions.

2H⁺ + 2e^–→  H₂

Hydrogen (H₂) forms bubbles on the metal surface. If the rate of hydrogen formation is very slow then a film of H₂ bubbles will be formed that will slow down the cathode reaction, hence the rate of corrosion will slow down.

If the rate of hydrogen production is very high then hydrogen molecules cannot form the film on the surface. So the corrosion proceeds rapidly.

2. Corrosion reactions between metals:

If two metals come in contact with a common aqueous medium then one metal will form an anode and the other will form a cathode. Now if both the metals are connected with a wire the reaction will proceed. Anode metal will be corroded and hydrogen will form at the cathode.

For example: 

If a zinc and a copper plate is immersed in an acidic medium then zinc will form an anode and will be corroded while hydrogen will be formed at the copper plate.

Anode reaction: Zn→ Zn⁺⁺ + 2e^–

Cathode reaction: 2H⁺ + 2e^–→ H²

So anode will be corroded and hydrogen will be evolved at the cathode.

3. Corrosion involving oxygen:

The oxygen dissolved in the electrolyte can react with accumulated hydrogen to form water. Depletion (reduction) of the hydrogen layer allows corrosion to proceed.

At cathode: O₂ + 2H₂→  2H₂O

The above reaction takes place in an acid medium. When the medium is alkaline or neutral oxygen is absorbed. The presence of moisture promotes corrosion.

Corrosion Types 

1. General Attack Corrosion:

It is also known as uniform attack corrosion, general attack corrosion is the most common type of corrosion and is caused by a chemical or electrochemical reaction.

• That results in the deterioration of the entire exposed surface of a metal.
• Ultimately, the metal deteriorates to the point of failure.
• General attack corrosion accounts for the greatest amount of metal destruction by corrosion but is considered as a safe form of corrosion, because it is predictable, manageable, and often preventable.

2. Localized Corrosion:

Unlike general attack corrosion, localized corrosion specifically targets one area of the metal structure. Localized corrosion is classified as one of three types:

• Pitting: Pitting results when a small hole, or cavity forms in the metal, usually as a result of the de-passivation of a small area.
  • This area becomes anodic, while part of the remaining metal becomes cathodic, producing a localized galvanic reaction.
  • The deterioration of this small area penetrates the metal and can lead to failure.
  • This form of corrosion is often difficult to detect because it is relatively small and may be covered and hidden by corrosion-produced compounds.

• Crevice corrosion: Similar to pitting, crevice corrosion occurs at a specific location. This type of corrosion is often associated with a stagnant micro-environment, like those found under gaskets and washerÿnd. clamps. Acidic conditions or a depletion of oxygen in a crevice can lead to crevice corrosion.

• Filiform corrosion: Occurring under painted or plated surfaces when water breaches the coating, filiform corrosion begins at small defects in the coating and spreads to cause structural weakness.

3. Galvanic Corrosion:

Galvanic corrosion, or dissimilar metal corrosion, occurs when two different metals are ‘ located together in a corrosive electrolyte. A galvanic couple forms between the two metals, where one metal becomes the anode and the other the cathode. The anode, or sacrificial metal corrodes and deteriorates faster than it would alone, while the cathode deteriorates more slowly than it would otherwise.

Three conditions must exist for galvanic corrosion to occur:

• Electrochemically dissimilar metals must be present.
• The metals must be in electrical contact.
• The metals must be exposed to an electrolyte.
• Subsurface Horizontal grain attack

4. Environmental Cracking:

Environmental cracking is a corrosion process that can result from a combination of. environmental conditions affecting the metal. Chemical, temperature and stress-related conditions can result in the following types of environmental corrosion:

• Stress Corrosion Cracking (SCC).
• Corrosion fatigue.
• Hydrogen-induced cracking.

5. Flow-Assisted Corrosion (FAC):

Flow-assisted corrosion, or flow-accelerated corrosion results when a protective layer of oxide on a metal surface is dissolved or removed by wind or water, exposing the underlying metal to further corroding and deterioration.

• Erosion-assisted corrosion.
• Impingement.
• Cavitation.

6. Intergranular corrosion:

Intergranular corrosion is a chemical or electrochemical attack on the grain boundaries of a metal. It often occurs due to impurities in the metal, which, tend to.be present in higher contents near grain boundaries. These boundaries can be more vulnerable to corrosion than the bulk of the metal.

7. De-Alloying:

De-alloying, or selective leaching is the selective corrosion of a specific element in an alloy. The most common type of de-alloying is the de-zincification of unstabilized brass. The result of corrosion in such cases is a deteriorated and porous copper.

8. Fretting corrosion:

Fretting corrosion occurs as a result of repeated wearing, weight, and/or vibration on an uneven, rough surface. Corrosion, resulting in pits and grooves, occurs on the surface. Fretting corrosion is often found in rotation and impact machinery, bolted assemblies, and bearings, as well as to surfaces exposed to vibration during transportation.

9. High-Temperature Corrosion:

• Fuels used in gas turbines, diesel engines and other machinery, which contain vanadium or sulfates can during combustion, form compounds with a low melting point.
• These compounds are very corrosive towards metal alloys normally resistant to high temperatures and corrosion including stainless steel.
• High-temperature corrosion can also be caused by high-temperature oxidization, sulfidation, and carbonization.

Corrosion Factors influencing 

The rate and extent of corrosion depends on the following factors:

Nature of the metal:

• Position in galvanic series: When two metals or alloys are in electrical contact in the presence of an electrolyte, the more active metal (or higher up in the series) suffers corrosion.  The rate and severity of corrosion depend upon the difference in their positions, and the greater the difference the faster is the corrosion of the anodic metal.
• Relative areas of the anodic and cathodic parts: When two dissimilar metals or alloys come in contact, the corrosion of the anodic part is directly proportional to the ratio of areas of the cathodic part and the anodic part.
• Purity of metal: Impurities in a metal generally form minute or tiny electrochemical cells and the anodic parts get corroded. For example, zinc metal containing impurity (such as Pb or Fe) undergoes corrosion of zinc, due to the formation of local electrochemical cells.
• The physical state of metal: The rate of corrosion is influenced by the physical state of the metal. The smaller the grain size of the metal or alloy, the greater its solubility and hence greater its corrosion. Nature of surface film: The ratio of the volume of the metal oxide to the metal is known as a “specific volume ratio.” The greater the specific volume ratio, the lesser the oxidation corrosion rate. According to the Pilling- bedworth rule the volume of oxide film is greater than the metal from which metal oxide is formed, then the film is protected.
• Solubility of corrosion products: In electrochemical corrosion, if the corrosion product is soluble in the corroding medium, then corrosion proceeds at a faster rate. On the contrary, if the corrosion product is insoluble in the medium or thereby suppresses further corrosion.
• Volatility of corrosion products: If the corrosion product is volatile, it volatilizes as soon as it is formed, thereby leaving the underlying metal surface exposed for environmental attack. This causes rapid and- continuous corrosion.

Corrosion Control Methods

Corrosion is a destructive and silent process operating all ‘the time, at all levels, and in all establishments. Since corrosion is impracticable to eliminate, effective Corrosion Science and Engineering lies in controlling rather than preventing it. Corrosion of metals occurs when they come in contact with a corrosive environment. Therefore, metallic corrosion can be prevented by either changing the metal (or) altering the environment separating the metal from the environment (or) by changing the electrode potential of the metal.

1. Design Improvement:

A large number of corrosion failures are due to improper design of equipment and corrosion control can be therefore warranted at the design stage itself. The usual procedure followed at the design stage is to:

• Establish basic requirements.
• Selecting the most suitable protective method and carrying out the final design work.

Some of the most general points for design are given below:

• Structures should have simplified forms. A complicated shape having more angles, edges, and internal surfaces will be easily corroded.
• Avoid crevices to avoid trapping of moisture and dirt which results in increased corrosion.
• Avoid residual moisture by having proper drainage holes and ventilation. Avoid contact with absorbent material.
• Avoid galvanic corrosion by using suitable electrical insulators. Cheap and easily exchangeable corroding pieces (or) paints where the contact of two different metals is unavoidable.

2. Change of Metal:

• Mostly corrosion protection involves bulk alloying (or) surface coatings. Surface coatings may pose problems related to adhesion, thermal expansion compatibility, etc.
• Surface processing of metals has been improved by iron implantation technique and laser treatment which results in a homogeneous and single-phase surface layer.
• Recently, electron beam surface area glazing has been found to increase the clear life of iron base tool materials.

3. Change of Electrode Potential of the Metal:

Corrosion can be prevented by changing the electrode potential by taking the metal to the immune region or passive region; According to the Pourbaix diagram, this can be accomplished by making the potential of the cathode equal to the open circuit potential of the anode.

1. Cathodic Protection:

Cathodic protection is defined as the reduction or prevention of corrosion by making it a cathode in the electrolytic cell.

• There are two methods of applying cathodic protection to metallic structures, such as galvanic or sacrificial anode and impressed current method.
• In each method, a direct current supply is more available for the protection of metal structures.
• The choice of the method to be used depends, upon several economic and technical considerations.

Galvanic or sacrificial anode:

•  It is possible to protect ship hulls from corrosion. An active metal, generally zinc is used as a sacrificial anode in contact with the corroding material.
• The two metals in contact form a galvanic cell, the terminals of which have been short-circuited.

 Impressed current method:

In of cathodic protection, an external source of direct current is connected to the structure to be protected (works as the cathode), and an auxiliary electrode functions as the anode (also called a consumable electrode).

• Some important impressed current anodes are graphite, scrap iron, platinum, and lead-silver alloys. Power sources used in these systems are rectifiers, batteries, etc. 
• The sacrificial anode system and impressed current anode system are complementary to each other.
• Cathodic protection can be applied to buried pipelines, underground cables, equipment for handling and storage of chemicals, steel structures in the marine atmosphere, hulls of ships, and oil-cargo-ballast tanks.

Some of the limitations of cathodic protection are:

• If polarization is too weak, materials remain exposed to a corrosive environment and remain unprotected.
• Results in stray-current corrosion in a neighboring unprotected buried structure. An application of cathodic current may lead to the destruction of passivity in certain passive alloys, such as stainless steel.
• If polarization is too high, certain metals such as lead and tin are attached by gasification, with the formation of gaseous hydrides, which can lead to the weakening and consequently disintegration of articles.

2. Anodic Protection:

Anodic protection is defined as the protection of a metal by maintaining it in a passive condition. This technique is based on the phenomenon of passivity. The metal to be protected is given a fixed potential to produce a passive film (of corrosion) on it and the structure is protected from a corrosive environment.

This method applies to metals which can obey the following conditions:

• The metal (or) alloy should have an active passive transition – For example:  Fe, Ni, Cr, Ti, etc.
• It must require only a small current to maintain passivity.
• The passive range for it must be wide.
• Sufficient electrical conductivity of the aggressive medium to which metal (or) alloy is exposed.
• The cathode is connected to the negative poles of the power source and completes the electrical circuit. Some of the cathodes used are platinum, clad brass, chromium, nickel, steel, etc.
• To measure the potential of the structures to be protected, a reference electrode is needed.
• The reference electrodes used are calomel, Ag/AgCI, Hg/HgSO_4, and Pt/PtO. These should be insoluble in corrosive fluid and have the potential that be stable concerning time.
• A potentiostat is necessary to maintain the potential at the required level.

Anodic Protection Advantages:

• In storage of ads.
• In fertilizer industries and some other chemical industries.

Anodic Protection  Limitations:

• This method applies only to a few metals that can be passive under certain environments.
• This requires costly instruments like potentiostat.

This method cannot be used for metals exposed to an environment containing aggressive anions such as chloride.

4. Using of coating:

Corrosion can be prevented by separating the metal from the corrosive environment by using protective coatings. Metallic and non-metallic coating are the. two types. The characteristics of these are:

• Good corrosion resistance.
• Perfect adherence to the underlying metal.
• Continuity to cover the metal surface completely.

Cathodic and anodic metallic coating provides a physical barrier between the environment and discontinuity in the coating will result in a localized attack,

For example Brass, chromium (or) gold coating on steel as a cathodic coating. Zinc and aluminum coating on steel as an anodic coating.

Material Handling Systems

Material handling systems in the pharma industry mainly involve the transportation of materials. The materials can be in any physical form like solid, liquid, or gas. So different types of handling instruments are required for different types of materials. Material handling is the movement, protection, storage, and control of materials and products throughout manufacturing, warehousing, distribution, consumption and disposal.

Material Handling Systems Integration:

Placing together several different materials handling technologies to create a complete functional system is important for any warehouse. Solutions contain as many or as few components as are required to accomplish the goals of your project, and the right combination can yield many benefits

Handling Of Solids

Handling Of Solids Conveyors: Clean-in-Place Conveying Systems:

Conveyors for medical and pharmaceutical warehouses are generally designed with specific requirements in mind, including ease of cleaning, disassembly, and maintenance.

• They must also be designed to meet containment level regulations.
• The types of conveyors available include those maximized for containment, systems integration for batch and continuous processing, and clean-in-place (CIP) designs.
• The clean-in-place option is popular because it allows virtually every component of the system to be easily cleaned without taking the conveyor apart.
• With CIP systems, cleaning is faster, requires less labor, is repeatable, and presents less risk of chemical exposure to workers.
• CIP systems are fully automated including features such as programmable logic, multiple balance tanks, valves, data acquisition, and custom spray nozzle systems.

When sanitary requirements are a factor, stainless steel conveyors are an option. These designs are also easy to clean and are designed to prevent cross-contamination.

Types of Conveyors:

Conveyors come in many shapes and sizes to meet just about any warehouse need.  Here’s a look at some commonly used conveyors:

• Pharmaceutical Belt Conveyor:  The belt conveyor is a simple solution that uses pulleys to quickly transport products along a belt. It is a popular choice because it’s easy to use and flexible. When configured specifically to your warehouse, belt conveyors are very economical because their speed and efficiency reduce labor costs without compromising accuracy

• Flexible/Extendable Conveyor: This is popular when versatile speed performance is needed. It can be installed in minutes and is ideal for fast loading and unloading of trucks and cost-effectiveness.
• Line-shaft Conveyor: This conveyor is a cost-effective solution to order transportation and accumulation requirements. It employs a line shaft with drive spools that line the shaft along the length of the conveyor. The spools have tensioned urethane bands that attach to gravity rollers; as the line shaft spins, it turns the spools, which then spin the urethane bands on the rollers, which causes them to turn. The spools are engineered to slip, which allows maximum accumulation without product damage.
• Heavy-duty Roller Conveyor System: This system delivers automation to the order fulfillment operation. Automation provides the benefits of systems-driven decision-making versus human-driven decision-making, resulting in better pick efficiencies, improved quality control, and lower process times.
• Vertical Conveyor: This is an excellent solution if you want to elevate a product within a small footprint. This type of conveyor can easily transport products between multiple levels speedily and safely. The conveyor system can be designed to meet specific space constraints using C- and S-shaped configurations. A vertical conveyor can accommodate up to 50 units per minute and can transport totes, cartons, trays, and pallets. It is designed for low maintenance, vibration-free, and quiet operation
• Spiral Conveyor: A spiral conveyor is great for transporting products between multiple elevations. It can handle a single infeed and single discharge and up to two or more discharges. It can be employed for lifting or lowering products. A continuous running belt results in high throughput with speeds of up to 200 FPM.
• Sortation Conveyor: This is an important part of an automated system. Sortation conveyor systems facilitate high product throughput, which is transported don dedicated lanes. The sortation logic is built upon specific business rules.

Handling Of Liquids In Pharmaceutical Industry

Pipes

• A pipe is a tubular section or hollow cylinder, usually but not necessarily of circular cross-section, used mainly to convey liquids and gases, slurries, powders, and masses of small solids. Pipes can be made up of metal alloys, ceramics, glass, plastics, etc.
• Pipes and tubings are specified in terms of their diameter and wall thickness. The diameter of steel pipes is the standard size.
• O.D. of all the pipes made with other materials also are matched with steel pipes. Therefore, these standard pipe sizes are called as IPS (Iron pipe size) or NPS (normal pipe size).
• The wall thickness of pipes is indicated by its schedule number which increases with the thickness. Ten schedule numbers 10, 20, 30, 40, 60, 80, 100, 120, 140, 160 are used.

Fittings

The fittings are used to join the two pipes. There are different types of fittings

• Screwed fittings: In this type ends of the pipe are threaded externally with the threading tool. The thread is tapered and the few threads farthest from the end of the pipe are imperfect so that a tight joint is formed when the pipe is screwed into the fitting.
• Flanged joints: The flanged joint design means that pipes are secured by external screws, providing additional joint support for the transportation of substances at high pressure.

• Welded joints: For joining large diameter pipes for high-pressure service welding is the standard method. Welding makes stronger joints than screwing and does not weaken pipe walls as occurs in screwed fitting. These joints are leakproof.

Valves

Valves are the components that are used to stop or regulate the flow of fluid in its path.

Different types of valves are available depending on their applications listed below:

• Gate valve, Plug valve, and Ball valve- used for isolation only. Globe valve- used for throttling.
• Check valve- used for preventing reverse flow (non-return).
• Butterfly valve- used for isolation as well as throttling.
• Diaphragm valve- used for isolation as well as throttling.

Pumping and compression

A pump is a mechanical device used to increase the energy of the liquid. In most of cases pump is used for raising fluid from a lower level to a higher level. Several pumps have been developed to meet a variety of operating conditions.

Airlift pump:

• An airlift pump is a pump that has low suction and moderate discharge of liquid and entrained solids.
• The pump injects compressed air at the bottom of the discharge pipe which is immersed in the liquid.
• The compressed air mixes with the liquid causing the air-water mixture to be less dense than the rest of the liquid around it and therefore is displaced upwards through the discharge pipe by the surrounding liquid of higher density.
• Solids may be entrained in the flow and if small enough to fit through the pipe, will be discharged with the rest of the flow at a shallower depth or above the surface.

Jet pumps:

• Jet pumps are centrifugal pumps with an ejector (venturi nozzle) attached at the discharge outlet.
• They function based on the venturi effect of Bernoulli’s principle utilizing constriction to reduce pressure and provide suction.
• After the pump is primed, a motive fluid is pumped through a standard centrifugal pump and enters an ejector.
• At the throat of the converging section of the ejector, the pressurized fluid is ejected at high velocity.
• This creates a low pressure (vacuum) at the throat, drawing the target fluid (from a well or other source) up into the nozzle.

Reciprocating pumps:

• A reciprocating pump essentially consists of a piston or plunger which moves to and fro inside a cylinder.
• The cylinder is connected to the suction and delivery tube each of which provides a nonreturn valve called the suction valve and delivery valve.
• During the backward motion of the piston, a partial vacuum is created inside the cylinder.
• Because of this low-pressure water will rise from the well through the suction tube and fill the cylinder by forcing it to open the suction valve.
• This operation is known as suction stroke. In

This stroke delivery valve will be closed and the suction valve will be open during this stroke. When the piston moves forward pressure is exerted on the liquid and due to this the suction valve closes and the delivery valve opens. The liquid is then forced up through the delivery pipe. This stroke is known as delivery stroke.

Materials Of Pharmaceutical Plant Construction Corrosion And Its Prevention Multiple Choice Questions

Question 1. A water attack test is performed on glass to find out the limits of

1. Acid liberated
2. Alkali liberated
3. Conductivity
4. Metal ions

Answer: 2. Alkali liberated

Question 2. Which one of the following is used m the construction of the outer jacket of the evaporating pan due to its low thermal conductivity?

1. Aluminium
2. Cast iron
3. Copper
4. Carbon steel

Answer: 2.  Cast iron

Question 3. Which metal makes steel corrosion-free?

• Chromium and Nickel
• Copper and Selenium
• Tantalum and Molybdenum
• Titanium and Niobium

Answer: 1.  Chromium and Nickel

Question 4. A severe form of corrosion that develops in highly localized areas of the metal surfaces is called________

• Erosion
• Galvanic corrosion
• Pitting corrosion
• Stress Corrosion

Answer: 3.  Pitting corrosion

Question 5. Which one of the following is not a measure to control corrosion?

• Increasing the temperature of storage
• Pumping inert gas into solution
• Removing air from boiler feed water
• Shortening the time of exposure

Answer: 1.  Increasing the temperature of storage

Question 6. In cathodic protection one of the following effects is suppressed

• Dissolution of anode
• Dissolution of cathode
• Dissolution of cathodic film
• Electric current

Answer: 2. Dissolution of cathode

Question 7. Which one of the following pumps are used when the liquid contains solids?

• Reciprocating pump
• Plunger pump
• Airjetpump
• Peristaltic pump

Answer: 2.  Plunger pump

Question 8. In n plunger pump, the moving element follows which one of the mechanisms?

1. One Direction
2. Propelling
3. Reciprocating
4. Rotating

Answer: 3.  Reciprocating

Question 9. Pumps are not used to increase one of the energy of liquids

1. Kinetic energy
2. Potential energy
3. Pressure energy
4. Radiant energy

Answer: 4.  Radiant energy

Question 10. The belt conveyor moves mainly with the help of

1. Drive pulley
2. Idlers
3. Non-troughing idlers
4. Snubber idler

Answer: 1. Drive pulley

Centrifugation In Pharmaceutical Engineering Introduction

Centrifugation is a common technique in the pharmaceutical industry used for the separation of constituents present in liquid with the help of centrifugal force.

Centrifugation is a technique that involves the application of centrifugal force to separate particles from a solution according to their size, shape, density, viscosity of the medium, and rotor speed. This process is used to separate two miscible liquids or solids from liquids.

The components that are dense in the mixture migrate away from the axis of the centrifuge, while less-dense components of the mixture migrate towards the axis. This process causes the formation of ‘pellet’ of the dense component at the bottom. The remaining solution (supernatant) may be discarded with a pipette.

There is a correlation between the size and density of a particle and the rate at the particle separates from a heterogeneous mixture when the only force applied is that of gravity. The larger the size and the larger the density of the particles, the faster they separate from the mixture.

By applying a larger effective gravitational force to the mixture, like a centrifuge, the separation of the particles is accelerated. This is ideal in industrial and lab settings because particles that would naturally separate over a long period can be separated in much less time (for evaluation purposes).

The rate of centrifugation is specified by the angular velocity usually expressed as revolutions per minute (RPM), or acceleration expressed as g. The most common application of centrifugation is the separation of solids from highly concentrated suspensions, which is used in the treatment of sewage sludges for dewatering where less consistent sediment is produced.

Centrifugation Objectives

• To separate the immiscible liquids.
• To purify the component by removing impurities in the supernatant liquid.
• To separate crystalline drugs from mother liquor.
• To test the emulsions and suspensions for creaming and sedimentation at accelerated speed.

Centrifugation Applications

• Production of bulk drugs:  After crystallization, the drugs are separated from the mother liquor by centrifugation. For example, traces of mother liquor is separated from aspirin crystals by centrifugation method.
• Production of biological products: The proteinaceous or other macromolecules remain in the water as colloidal dispersion during their manufacturing it is difficult to separate them by common methods of separation
• Evaluation of suspensions and emulsions: One of the problems of suspensions is sedimentation and one of the problems of emulsions is creaming. These do not occur immediately after formulation. These problems develop over time. So quick evaluation of these problems can be done by enhancing the speed of creaming and sedimentation by centrifuge machine.
• Determination of molecular weight of colloids: Polymers, proteins, and such macromolecules often form colloidal dispersions. The molecular weights of that molecule can be determined by ultracentrifugation. The larger molecules will be arranged at the periphery and the lighter molecules near the center.

Other applications:

• Separating chalk powder from water.
• Removing fat from milk to produce skimmed milk.
• Separating particles from an air-flow using cyclonic separation.
• The clarification and stabilization of wine.
• Separation of urine components and blood components in forensic and research laboratories.
• Aids in the separation of proteins using purification techniques such as salting out, For example: ammonium sulfate precipitation.

Centrifugation Principle

The centrifuge involves the principle of sedimentation, where the acceleration at centrifugal force causes denser substances to separate along the radial direction at the bottom of the tube.

By the same concept lighter objects will tend to move to the top of the tube; in the rotating picture, move to the center.

• In a solution, particles whose density is higher than that of the solvent sink (sediment), and particles that are lighter than it float to the top. The greater the difference in density, the faster they move.
• If there is no difference in density (isopycnic conditions), the particles stay steady.
• To take advantage of even tiny differences in density to separate various particles in a solution, gravity can be replaced with the much more powerful “centrifugal force” provided by a centrifuge.
• Particles having a size above 5 pm sediment at the bottom due to gravitation force.
• Such a suspension can be separated by simple filtration techniques.
• If the size of particles is less than 5 pm they undergo Brownian motion. In such suspension, a stronger centrifugal force is applied to separate the particles.
• It is convenient to measure the centrifugal force in terms of ratio to the gravitational force, that is the number of times the centrifugal force is greater than the gravitational force.
• Let us consider a body of mass m rotating in a circular path of radius rat a velocity of ‘V’.

The force acting on the body in a radial direction is given by:

F = mv²/R

Where,

F = Centrifugal force

m = Mass of body

v = Velocity of the body

R = Radius of the circle of rotation

The gravitational force acting upon the same body G = mg.

Where,

G = Gravitational force

g = Acceleration due to gravity

The centrifugal effect is the ratio of the centrifugal force and gravitational forces so that

Centrifugal force = Force acting radially/ Gravitational force

C = F/G

= mv²/mgr

= v² / gr

Since, v = 2πrn

Where,

n = Speed of rotation (r.p.m)

Where,

d is the diameter of rotation

G = 9.807 m/s²

Centrifugal effect = 2.013 n²d

When n is expressed in s’1 and d is in meters.

From the equation, it is clear that the centrifugal effect is directly proportional to the diameter and the square of the speed of rotation. So to increase the centrifugal effect, it is advantageous to use a centrifuge of the same size at a higher speed, rather than using a larger centrifuge at the same speed.

Principle Applications:

If the particles of suspensions are very small then a high centrifugal effect will be required to separate the particles. To separate such suspensions the size of the centrifuge is kept smaller but it is rotated at a very high speed (rpm). If a large amount of material is to be separated and a low centrifugal effect is sufficient to separate the suspension then the diameter of the centrifuge is increased and speed (n) is kept low.

Types Of Centrifugal Separations

There are two types of centrifugal techniques for the separation of particles; differential centrifugation and density gradient centrifugation. Density gradient centrifugation can further be divided into rate-zonal and isopycnic centrifugation.

Differential Centrifugation:

The simplest form of separation by centrifugation is differential centrifugation, sometimes called differential pelleting. Particles of different densities or sizes in a suspension will sediment at different rates, with the larger and denser particles sedimenting faster.

These sedimentation rates can be increased by using centrifugal force. A suspension of cells subjected to a series of increasing centrifugal force cycles will yield a series of pellets containing cells of decreasing sedimentation rate.

Particles of different densities or size will sediment.

At different rates with the largest and most dense particles sedimented the fastest followed by less dense and smaller particles.

• Differential pelleting is commonly used for harvesting cells or producing crude subcellular fractions from tissue homogenate.
  • For example: Arat liver homogenate containing nuclei, mitochondria, lysosomes, and membrane vesicles that are centrifuged at low speed for a short time will pellet mainly the larger and more dense nuclei.
• Subsequent centrifugation at a higher centrifugal force will pellet particles of the next lower order of size
  • For example: Mitochondria
• It is unusual to use more than four differential centrifugation cycles for a normal tissue homogenate. Due to the heterogeneity in biological particles, differential centrifugation suffers from contamination and poor recoveries.

Contamination by different particle types can be addressed by resuspension and repeating the centrifugation steps (i.e., washing the pellet).

Density Gradient Centrifugation:

Density gradient centrifugation is the preferred method to purify subcellular organelles and macromolecules. Density gradients can be generated by placing layer after layer of gradient media such as sucrose in a tube with the heaviest layer at the bottom and the lightest at the top in either a discontinuous mode.

The cell fraction to be separated is placed on top of the layer and centrifuged. Density gradient separation can be classified into two categories, rate- zonal (size) separation and isopycnic (density) separation.

1. Rate-Zonal Centrifugation:

In rate-zonal centrifugation, the problem of cross-contamination of particles of different sedimentation rates may be avoided by layering the sample as a narrow zone on top of the density gradient.

• In this way, the faster sedimenting particles are not contaminated by the slower particles as occurs in differential centrifugation.
• However, the narrow load zone limits the volume of the sample (typically 10%) that can be accommodated on the density gradient.
• The gradient stabilizes the bands and provides a medium of increasing density and viscosity.

The sample is layered as a narrow zone on the top of a density gradient (2). Under centrifugal force, particles move at different rates depending on their mass (3). The speed at which particles sediment depends primarily on their size and mass instead of density. As the particles in the band move down through the density medium, zones containing particles of similar size form as the faster sedimenting particles move ahead of the slower ones. Because the density of the particles is greater than the density of the gradient, all the particles will eventually form a pellet if centrifuged long enough.

2. Isopycnic Centrifugation: 

In isopyclic separation, also called buoyant or equilibrium separation, particles are separated solely based on their density.

• Particle size only affects the rate at which particles move until their density is the same as the surrounding gradient medium.
• The density of the gradient medium must be greater than the density of the particles to be separated.
• By this method, the particles will never sediment to the bottom of the tube, no matter how long the centrifugation time is given.
• Starting with a uniform mixture of sample and density gradient under centrifugal force, particles move until their density is the same as the surrounding medium (2).

Upon centrifugation, particles of specific density sediment until they reach the point where their density is the same as the gradient media (i.e., the equilibrium position).

• The gradient is then said to be isopycnic and the particles are separated according to their buoyancy.
• Since the density of biological particles is sensitive to the osmotic pressure of the gradient, isopycnic separation may vary significantly depending on the gradient medium used.
• Although a continuous gradient may be more suited for analytical purposes, preparative techniques commonly use a discontinuous gradient in which the particles band at the interface between the density gradient layers.
• This makes harvesting certain biological particles (For example:, lymphocytes) easier.

Centrifuges

A centrifuge is a mechanical device that can subject an experimental sample to a sustained centrifugal force.

• Tubes containing experimental samples either in suspension or dissolved in a fluid can be “spun” at high speeds for particular lengths of time to achieve particular objectives.
• In bioresearch labs, these objectives include the separation, concentration, clarification, characterization, and purification of biological and biochemical materials.
• Two major components of a centrifuge are the drive mechanism and the rotor. The drive mechanism is the source of rotary motion and is powered by an electric motor, by air pressure, or by turbines, depending upon the type of centrifuge.
• The rotor is the large rotating element of a centrifuge into or onto which samples are loaded. It is driven about a fixed axis (or shaft) by the drive mechanism, with the expenditure of a large amount of energy.
• A loaded rotor must be well-balanced about its axis of rotation, to minimize vibration and strain on the shaft.

Centrifuge Types:

1. Speed:

The speed of a centrifuge is measured in revolutions per minute or rpm. Centrifuges are generally divided into 3 categories based on their maximum attainable speed:

1. Low speed to a maximum of ~ 5 × 10³ rpm.
2. High speed to a maximum of ~2 × 10⁴ rpm.
3. Ultracentrifuges to maximum of ~10⁵ rpm.

2. Temperature:

Centrifuges are either refrigerated or non-refrigerated. Refrigerated centrifuges have a built-in refrigeration unit surrounding the rotor, with a temperature sensor and thermostat permitting the selection of a particular temperature or a permissible temperature range that is maintained during centrifugation. Many biological samples are temperature sensitive, and centrifugation in the cold (say, 1-4°C) is frequently required

Centrifuges that are not refrigerated are normally used at whatever temperature the room they are in happens to be.

Types of Rotors:

There are two fundamental types of rotors:

1. Fixed-angle rotors, and

2. Swinging bucket rotors.

1. Fixed-angle rotor: In fixed-angle rotors, the tubes containing samples are placed into shields or openings in the rotor at one particular pre-set angle. The tubes are thus tilted with their tops closer to the shaft than their bottoms, and remain in that fixed position during the run, regardless of rotor speed.
2. Swinging-bucket rotor: In swinging bucket rotors, the tubes are initially vertical. The bottom of the sample tubes then swing outward freely as the shaft rotates, and the tubes are horizontal during the run. By the time the centrifuge stops, however, the tubes have returned to their starting vertical position. Swinging-bucket rotors are particularly useful for sedimenting a sample through a density gradient

A major advantage is that the density gradient solution (usually sucrose or cesium chloride) can be put into the centrifuge tubes vertically, while centrifugation takes place with the tubes in a horizontal position. Sedimented materials then appear as parallel bands running across the width of the tube, whereas, in a fixed-angle rotor, the bands would be diagonal. In the latter case there is a reorientation of contents upon removal of tubes from the rotor, whereas no reorientation of tube contents occurs with swinging bucket rotors.

Classification Of Industrial Centrifuges In Pharmaceutical Engineering

1. Perforated bowl or filter types

• Batch type
• Top-driven
• Under-driven
• Semicontinuous
• Continuous

2. Solid-bowl or sedimentation types

• Vertical
• Simple bowl
• Bowl with plates
• Horizontal
• Continuous decanters

Perforated Basket Centrifuge In Pharmaceutical Engineering

Depending on the arrangement of the perforated basket these instruments have two different names.

• If the basket is mounted above a driving shaft it is called a driven centrifuge.
• If the basket is suspended from a shaft it is called as top-driven centrifuge.

Perforated Basket Centrifuge Principle:

A perforated basket centrifuge is a filtration centrifuge. The separation is through a perforated wall based on the difference in the densities of solid and liquid phases. The basket has a perforated side wall. During centrifugation, the liquid phase passes through the perforated wall, while the solid phase is retained in the basket. The solid is removed after cutting the sediment by a blade after stopping the centrifuge.

1. Top driven centrifuge:

Top-driven centrifuge Construction:

It consists of a rotating basket suspended on a vertical shaft and driven by a motor from the top. The sides of the basket are perforated and are also. covered with a screen on the inside. Surrounding the basket is a stationary casing that collects the filtrate.

Top-driven centrifuge Working:

This machine is a batch-type machine. The material (suspension) is put into the basket. Then power is applied. The basket accelerates to its maximum speed. The particles and liquid are thrown by centrifugal force to the wall of the basket.

The liquid passes out through the screen and the solid particles are retained on the screen as deposit. After a definite time, the power is turned off, a brake applied, and the basket brought to rest. The discharge valve at the bottom of the basket is raised, and the deposited solid is cut from the side of the basket into the opening

2. Under driven centrifuge:

Under driven centrifuge Construction:

It consists of a rotating basket placed on a vertical shaft and driven by a motor from the bottom. The sides of the basket are perforated and are also covered with a screen on the inside. Surrounding the basket is a stationary casing that collects the filtrate.

Under driven centrifuge Working:

This machine is a batch-type machine. The material (suspension) is put into the basket. Then power is applied. The basket accelerates to its maximum speed. The particles and liquid are thrown by centrifugal force to the wall of the basket. The liquid passes out through the screen and the solid particles are retained on the screen as deposit.

After a definite time, the power is turned off, a brake is applied, and the basket is brought to rest. The cover at the top of the basket is raised, and the deposited solid is cut from the side of the basket and collected.

Under driven centrifuge Use:

• Crystals can be separated from mother liquor. Liquids can be clarified by removing unwanted solids, and dirt from oils.
• In cloth industries after washing the liquid is strained and the cloths are taken out from the top cover.

Under driven centrifuge Advantages:

• The centrifuge is very compact and occupies very little floor place.
• It can handle slurries with a high proportion of solids and even those having paste-like consistency.
• The final product has a very low moisture content.
• In this method, the dissolved solids are separated from the cake.
•  It is a fast process.

Under-driven centrifuge Disadvantages:

• The entire cycle is complicated resulting in considerable labour costs.
• It is a batch process.
• If the machine is adapted for prolonged operation, there is considerable wear and tear of the equipment.
• On prolonged operation, the solids may form hard cake, due to the centrifugal force, which is difficult to remove simultaneously

Semi-Continuous Centrifuge In Pharmaceutical Engineering

Semi-continuous centrifuge Principle:

A semi-continuous centrifuge is a filtration centrifuge. The separation is done based on the difference in the densities of the solid and liquid. This separation occurs through a perforated wall. The bowl contains a perforated side wall. During centrifugation, the liquid phase passes through the perforated wall, while the solid phase remains in the bowl. The solid is washed and removed by cutting the sediment using a blade.

Semi-continuous centrifuge Construction:

It consists of a rotating basket placed on a horizontal shaft and driven by a motor from side. The side of the basket is perforated. Surrounding the basket is a stationary casing that collects the filtrate, Slurry is introduced through a pipe that enters the basket through the center.

To wash the crystal the wash-pipe is also introduced through the center of the basket. The layer of cake is removed by a chute fitted with a knife. The knife, cuts down the cake within the basket. The knife-chute assembly is raised with the help of a hydraulic apparatus.

Semi-continuous centrifuge Working:

The basket is rotated horizontally by a motor. The slurry is introduced through the slurry entry pipe. The liquid passes out through the perforated side. The crystals remain within the basket. When the cake height is about 2 – 3 inches the slurry entry is stopped by a “feeler diaphragm valve assembly”.

The basket rotates at a predetermined time then the cake is washed with water. The basket is rotated for another predetermined time. After that the hydraulic apparatus raises the knife-chute assembly to cut the cake. The cake is collected through the chute.

Semi-continuous centrifuge Use:

• This is a semi-continuous type of centrifuge.
• Crystals can be separated from mother liquor.
• Liquids can be clarified by removing unwanted solids and dirt from oils.

Semi-continuous centrifuge Advantages:

Short-cycle automatic batch centrifuge is used when solids can be drained fast from the bowl.

Semi-continuous centrifuge Disadvantage:

• During discharge, considerable breakage of crystals is possible.
• Many moving parts are involved making the construction and functioning more complicated.

Non-Perforated Basket Centrifuge In Pharmaceutical Engineering

Non-perforated Basket Centrifuge Principle:

This is a sedimentation centrifuge. The separation is based on the difference in the densities of solid and liquid phases without a porous barrier. The basket contains a non-perforated side wall during centrifugation, solid phase is retained on the sides of the basket; while the liquid remains at the top, which is removed by a skimming tube.

Non-perforated Basket Centrifuge Construction:

It consists of a metallic basket. The basket is suspended on a vertical shaft and is driven by a motor using a suitable power system.

Non-perforated Basket Centrifuge Working:

The suspension is fed continuously into the basket. During centrifugation, the solid phase is retained on the sides of the basket, while the liquid remains on the top. The liquid is removed over a weir or through a skimming tube.

When a suitable depth of solids has been deposited on the walls of the basket, the operation is stopped. The solids are then scraped off by hand or using a scraper blade

Non-perforated Basket Centrifuge Use:

Non-perforated basket centrifuge is useful when the deposited solids offer high resistance to the flow of liquid.

 Super Centrifuge In Pharmaceutical Engineering

 Super Centrifuge Principle:

It is a solid bowl-type continuous centrifuge used for separating two immiscible liquid phases. It is a sedimentation-type centrifuge. During centrifugation, the heavier liquid is thrown against the wall of the bowl while the lighter liquid remains as an inner layer. The two layers are simultaneously separated

 Super Centrifuge Construction:

It consists of a long, hollow, cylindrical bowl of small diameter. The bowl is suspended from a flexible spindle at the top and the bottom is fitted loosely in a bush. It is rotated on its vertical axis.

Feed is introduced through the bottom through a nozzle. Two liquid outlets are provided at different heights. Inside the bowl, there are three baffles to catch the liquid and force it to travel at the same speed of rotation as the bowl wall.

 Super Centrifuge Working:

The centrifuge is allowed to rotate on its vertical axis at about 2000 rpm. The feed is introduced at the bottom through a nozzle under pressure. During centrifugation, two liquid phases separate based on their densities.

The heavier liquid moves towards the periphery and the lighter liquid forms an inner layer. Both liquids climb to the top of the vertical bowl. These two layers are simultaneously separately removed from different heights through modified outlets.

 Super Centrifuge Use:

Super centrifuge is used for separating liquid phases of emulsions in foods and pharmaceuticals.

Centrifugation In Pharmaceutical Engineering Multiple Choice Questions

Question 1. Which property of substance influences centrifugation?

1. Surface area
2. Density
3. Interfacial tension
4. Melting point

Answer: 2. Density

Question 2. Centrifugation is used for

1. Mixing
2. Purification
3. Separation
4. Sizing

Answer: 3.  Separation

Question 3.  The solid that has high specific gravity will remain in which location after centrifugation?

1. Bottom
2. Top
3. Middle
4. Side of these

Answer: 1. Bottom

Question 4.  For sedimentation type, the centrifuge has one of the following conditions

1. Basket is non-perforated
2. Basket is perforated
3. Containing filter aid
4. Containing filter medium

Answer: 1.  Basket is non-perforated

Question 5. Centrifuges are used for the analysis of dosage forms to analyze:

1. Physical stability
2. Chemical stability
3. Photostability
4. Thermal stability

Answer: 1. Physical stability

Question 6. What are the two general types of centrifuge devices for solid-liquid separations?

1. Sedimentation centrifuges, filtering centrifuges
2. Sedimentation centrifuges, decantation centrifuges
3. Filtering centrifuges, sintering centrifuges
4. Sedimentation centrifuges, two-way centrifuges

Answer: 1. Sedimentation centrifuges, filtering centrifuges

Question 7. After centrifugation when the sublimate settles, clear liquid

1. Can be allowed to rest
2. Can be allowed to form crystals
3. Can be decanted off
4. Can be evaporated

Answer: 3. Can be decanted off

Question 8. The unit for measurement of the velocity of the centrifuge is

1. Diameter of rotation
2. Meter/sec²
3. Meter square per second
4. Revolutions per minute

Answer: 4. Revolutions per minute

Question 9. Which factor from the following does not affect the centrifugation?

1. Centrifugation time
2. Viscosity of slurry
3. Speed of centrifuge
4. Temperature

Answer: 4.  Temperature

Question 10. During discharge breaking of crystals is possible in

1. Horizontal continuous centrifuge
2. Non – Perforated basket centrifuge
3. Semi-continuous centrifuge
4. Super centrifuge

Answer: 3. Semi-continuous centrifuge

Filtration In Pharmaceutical Engineering Introduction

Filtration may be defined as the separation of a solid from a fluid using a porous medium that retains the solid but allows the fluid to pass. Filtration is usually more expensive than sedimentation, but if has the advantage that it is applicable without regard to density differences and it allows enhanced separation.

The liquid produced after filtering is called filtrate, while the solid remaining in the filter is called residue (retentate, filtrate) or filter cake. The filtering device or the material of the filter is called the filter medium. In such cases, periodical or steady residue removal has to be ensured in the course of filtering operations.

The term fluid includes liquids and gases, so that both may be subjected to filtration. The suspension of solid and liquid to be filtered is known as the “slurry”. The porous medium used to retain the solids is described as the filter medium; the accumulation of solids on the filter is referred to as the filter cake, while the clear liquid passing through the filter is the filtrate.

Filtration In Pharmaceutical Engineering Objectives

• To eliminate contaminant particles to recover dispersing fluid.
• To recover solid particles by eliminating the dispersing fluid.
• To maintain the safety of parenteral solutions by eliminating particulate matter from parenteral solution.
• To provide high-quality water for workers as well as for the processing of pharmaceuticals.
• To separate the reaction mixture from the final product after a chemical reaction.
• To sterilize the solutions containing heat-sensitive drugs by using bacteria-proof filters.

Filtration Applications In Pharmaceutical Engineering

Filtration is used to separate particles and fluid in a suspension, where the fluid be a liquid, a gas, or a supercritical fluid. Depending on the application, either one or both of the components may be isolated.

Filtration, as a physical operation, is very important in chemistry

• Materials of different chemical compositions.
• A solvent is chosen which dissolves the component, while not dissolving the other.
• By dissolving the mixture in the chosen solvent, one component will go into the solution and pass through the filter, while the other will be retained.
• This is one of the most important techniques used by chemists to purify compounds.
• Filtration is also important and widely used as one of the unit operations of pharmaceutical technology.
• It may be simultaneously combined with other unit operations to process the feed stream, as in the bio-filter, which is a combined filter and biological digestion device.
• Production of sterile products: In sterile manufacturing, there is a need for a pure and
  particle-free air which is fulfilled by the HEPA filters. Also for sterilization of
  solutions containing heat-sensitive drugs bacteria-proof filters are used.
• Eye drops are sterilized by the filtration.
• In the production of drugs after a chemical reaction, the final drug is separated from the reaction mixture by filtration.
• Filtration is an essential step in oral liquid formulations such as elixirs, aromatic waters, syrup, etc.
• Waste solids must be separated from the waste liquid before its disposal

Filtration Mechanisms

The mechanisms whereby particles are retained by the filter are of significance only in the early stages of liquid filtration, as a rule. Once a preliminary layer of particles has been deposited, the filtration is effected by the filter cake, the filter medium serving only as a support.

1. Straining: The simplest filtration procedure is “straining”, in which, like sieving, the pores are smaller than the particles, so that the latter are retained on the filter medium
2.  Impingement: If the filter medium is cloth with a nap or is porous, then particles get entangled in the mass of fibers. It occurs due to the smaller size of particles than the pores.
3. Entanglement: If the filter medium consists of a cloth with a nap or a porous felt, then particles become entangled in the mass of fibers. Usually, the particles are smaller than the pores, so impingement may be involved.
4. Attractive Forces: In certain circumstances, particles may collect on a filter medium as a result of attractive forces. The ultimate in this method is the electrostatic precipitator, where large potential differences are used to remove the particles from air streams. In practice, the process may combine the various mechanisms, but the solids removal is affected normally by a straining mechanism once the first complete layers of solids has begun to form the cake on the filter medium.

Filtration Theories

The flow of liquid through a filter follows the basic rule that governs the flow of any liquid through the medium offering resistance.

The rate of flow may be expressed as:

Rate= Driving force/Resistance

The rate of filtration may be expressed as volume (liter) per unit time (dv/dt). The driving
force is the pressure difference between the upstream and downstream of the filter. The resistance is not constant. It increases with an increase in the deposition of solids on the filter medium. Therefore filtration is not steady state.

The rate of flow will be greatest at the beginning of the filtration process since the resistance is minimal. Once the filter cake is formed, its surface acts as a filter medium, and solids continuously deposit adding to the thickness of the cake

Resistance to movement = Press upstream-downstream /Length of capillaries

1. The Hagen – Poiseuille law is applicable in the case of laminar, frictional, and temporally constant flow. According to this, filtration can be considered a flow flowing through parallel capillaries.

The average rate is one-half of the maximum rate:

V = V_max /2 = r⁴ πΔp/8ηL

Where,

V is the rate of flow

r is the radius of capillary,

h is the viscosity of the liquid,

L is the length of the capillary.

Δp is the pressure difference across the filter,

η is the viscosity of the filtrate,

2. Darcy studied the flow of liquids through granular media at constant pressure and established that the filtration rate is,

dV/dt= BAΔp_i/η L

Where,

V is the volume of filtrate,

t is the duration of filtration,

B is the permeability constant of the filter bed,

A is filter surface,

Δp_i a drop of pressure on the filter bed,

η dynamic viscosity of filtrate,

L width of the filter bed

3. The Kozeny-Carman relation applies to laminar flow passing through agglomerated particles. According to the model, the permeability constant is:

Where,

ε porosity,

η viscosity,

k Kozeny-Carman constant,

l_i width of sludge cake,

a_f specific surface of particles.

Factors Affecting Rate Of Filtration

1. Permeability coefficient:

The constant (K) represents the resistance of both the filter medium and the filter cake. As the thickness of the cake increases, the rate of filtration will decrease. Also, the surface area of the particles, the porosity of the cake, and the rigidity or compressibility of the particles could affect the permeability of the cake.

2. Area of filter medium:

The total volume of filtrate flowing from the filter will be proportional to the area of the filter. The area can be increased by using larger filters. In the rotary drum filter, the continuous removal of the filter cake will give an infinite area for filtration.

3. Pressure drop:

The rate of filtration is proportional to the pressure difference across both the filter medium and filter cake.

The pressure drop can be achieved in several ways:

• Gravity: A pressure difference could be obtained by maintaining a head of slurry above the filter medium. The pressure developed will depend on the density of the slurry.
• Vacuum: The pressure below the filter medium may be reduced below atmospheric pressure by connecting the filtrate receiver to a vacuum pump and creating a pressure difference across the filter.
• Pressure: The simplest method is to pump the slurry into the filter under pressure.
• Centrifugal force: The gravitational force could be replaced by centrifugal force in particle separation,

4. The viscosity of filtrate:

It would be expected that an increase in the viscosity of the filtrate will increase the resistance of flow so that the rate of filtration is inversely proportional to the viscosity of the fluid.

This problem can be overcome by two methods:

• The rate of filtration may be increased by raising the temperature of the liquid, which lowers its viscosity. However, it is not practicable if thermolabile materials are involved or if the filtrate is volatile.
• Dilution is another alternative but the rate must be doubled.

5. Thickness of filter cake:

The rate of flow of the filtrate through the filter cake is inversely proportional to the thickness of the cake. Preliminary decantation may be useful to decrease the amount of the solids.

6. Pore size of filter media:

The rate of filtration is directly proportional to the pore size of the filter media. The liquid having coarse particles requires a coarse filtering media to remove them. So, the rate of filtration is increased when a coarse filter medium is used for filtration.

7. Temperature of the liquid:

Temperature plays an important role in rate of filtration. The viscosity of liquid is reduced due to an increase in the temperature. So, the speed of the filtration will increase with the increase in temperature.

Filter Media

Filter medium is a surface where solids are deposited during filtration forming a cake and which also provides mechanical support for the filter cake.

Ideal Properties of Filter Media:

• It should be chemically inert.
• It should have high retention power.
• It should have sufficient mechanical strength.
• It should not absorb dissolved substances.
• It should be resistant to corrosive action.

Selection of Filter Media Depends on:

• Size of particles to be filtered.
• Amount of liquid to be filtered.
• Nature of product to be filtered.

Filter media may be either flexible or inflexible:

1. Flexible: Flexible For the filtration of chemically aggressive fluids and for filtration at elevated temperatures or large mechanical stresses. Flexible media also may be non-metallic barriers consisting of cloth or unwoven fibers. Such non-metallic media may be made of asbestos, glass, cotton, wool, or poly-vinyl chloride.
2. Inflexible: Inflexible media include rigid disks, slabs, canisters, and sheets made by molding and sintering powdered ceramics, metals, glass, or synthetic materials. Such media also may consist of beds of unconsolidated particles of stone, coal, charcoal, coke, diatomaceous earth, sand, or clay.

Different Types of Filter Media Used

• Woven materials: Woven materials are made up of cotton, silk, glass metal, etc. Synthetic fibers are more resistant to chemicals as compared to natural fibers.
• Perforated sheet metal: The stainless steel plates have pores that act as channels as in the case of metafilter.
• Bed of granular solid: Build up on supporting medium: In some processes a bed of graded solids may be formed to reduce the resistance to the flow. e.g. graval, asbestos.
• Prefabricated porous solid unit: Porous solids are prefabricated into a single unit and are being increasingly used for their convenience and effectiveness, e.g. sintered glass filter.
• Membrane filter media: These are basic tools for micro-filtration, useful in the preparation of sterile solutions. These filters are made by casting various esters of cellulose, or from nylon, Teflon, and polyvinyl chloride. The filter is a thin membrane with millions of pores per square centimeter of filter surface.

Filter Aids

Filter aid can be defined as an agent consisting of solid particles that improve filtering efficiency (as by increasing the permeability of the filter cake) and that is either added to the suspension to be filtered or placed on the filter as a layer through which the liquid must pass.

These are fine, chemically inert powders used in filtration to maintain high flow rates while giving brilliant clarity. The objective of the filter aid is to prevent the medium from becoming blocked and to form an open, porous cake, so reducing the resistance to the flow of the filtrate. The particles must be inert, insoluble, incompressible, and irregularly shaped.

Filter Aid Mechanism of Action:

Filter aids impart rigidity and porosity to the cake due to their peculiar irregular shape, low surface area and narrow particle size distribution. The rigid structure provides support for the compressible particles in the slurry.

Filter Aid Ideal Properties :

• It should be chemically inert to the liquid being filtered
• It should be free from impurities.
• It should have low specific gravity, so that filter aids remain suspended in liquid.
• It should be recoverable.
• It should form a porous cake.
• It should be insoluble in liquids

The common filter aids are diatomaceous earth (DE), perlite, cellulose and others. Diatomaceous earth (DE) is the skeleton of ancient diatoms.

They are mined from ancient seabed, processed, and classified to make different grades of filter aids.

• DE is the most commonly used filter aid today. However, the crystalline type DE is a suspicious carcinogen and inhalation needs to be avoided during handling.
• There are different grades of commercial DE. A finer grade may be employed to increase the clarity of the filtrate.
• The smaller the filter aid particle size, the smaller the process particles can be removed.
• However, the filtration rate is lower. There is always a balance between initial filtrate clarity and filtration rate.
• The particle size captured by various filter aids may also vary because of liquid viscosity, surface charge, etc.
• Perlite is another important mineral filter aid. It is a particular variety of naturally occurring glassy volcanic rock, characterized by onion-like, splintery breakage planes.
• After crushing and heating, this rock will expand explosively to about ten times its original volume.
• Diatomaceous earth and perlite are silica-based minerals. There are several other special materials used as filter aids, including asbestos, cellulose, agricultural fibers, sawdust, rice hull ash, paper fibers etc.
• Cellulose can be used for filtration systems that cannot tolerate silica. The filterability of cellulose is much worse than DE or perlite but cellulose can be incinerated as well as provides better cake integrity

Filter Aid Disadvantages: 

• Sometimes coloring active substances get adsorb on the filter aids.
• Rarely, filter aids cause contamination such as soluble iron salts.
• Liquid retained in the pores of filter cake is getting lost.

Classification Of The Filtration Equipment

Equipment is are classified as follows:

1. Based on the application of external force:
   • Pressure filters: Plate and frame filter press and MetaFilter.
   • Vacuum filters: Filter leaf.
   • Centrifugal filters.
2. Based on the operation of the filtration:
3. Continuous filtration: Discharge and filtrate are separated steadily and uninterrupted
4. Discontinuous filtration: Discharge of filtered solids is intermittent. Filtrate is removed continuously. The operation must be stopped to collect the solids.
5. Based on the nature of filtration:
6. Cake filters: Remove large amounts of solids (sludge or crystals).
7. Clarifying filters: Remove small amounts of solids.
8. Cross-flow filters: Feed of suspension flows under pressure at a fairly high velocity across the filter medium.

Equipments Of Pharmaceutical Interest

• Sand filters
• Filter presses: chamber, plate, and frame filters (non-washing/washing; closed delivery/open delivery).
• Leaf filters.
• Edge filters: Streamline and meta filters.
• Rotary continuous filters.
• Membrane filters.

Plate And Frame Filter Press

Plate And Frame Filter Press Principle:

The mechanism is surface filtration. The slurry enters the frame by pressure and flows through the filter medium. The filtrate is collected on the plates and sent to the outlet. Several frames and plates are used so that surface area increases and consequently large volume of slurry can be processed simultaneously with or without washing.

Plate And Frame Filter Press Construction:

• The filter press is made of two types of units, plates and frames.
• Frame: Maintains the slurry reservoir, inlet (eye) for slurry.
• Filter medium.
• The plate along with supporting the filter medium, receiving the filtrate and outlet (eye).
• Assembly of plate and frame filter press.

These are usually made of aluminum alloy. Sometimes these are also lacquered for protection against corrosive chemicals and made suitable for steam sterilization.

• The frame contains an open space inside wherein the slurry reservoir is maintained for filtration and an inlet to receive the slurry.
• It is indicated by two dots in the description. The plate has a studded or grooved surface to support the filter cloth and an outlet. It is indicated by one dot in the description.
• The filter medium (usually cloth) is interposed between the plate and frame.
• Frames of different thicknesses are available. It is selected based on the thickness of the cake formed during filtration.
• The optimum thickness of the frame should be chosen.
• The plate, filter medium, frame, filter medium, and plate are arranged in the sequence and clamped to a supporting structure. It is normally described by dots as 1.2.1.2.1 so on.
• A number of plates and frames are employed so that the filtration area is as large as necessary. In other words, a number of filtration units are operated in parallel.
• Channels for the slurry inlet and filtrate outlet can be arranged by fitting eyes to the plates and frames, these join together to form a channel.
• In some types, only one inlet channel is formed, while each plate has individual outlets controlled by valves.

Plate And Frame Filter Press Working:

The working of the frame and plate process can be described in two steps, namely filtration and washing of the cake (if desirable).

1. Filtration operation:

• Slurry enters the frame from the feed channel and passes through the filter medium on to the surface of the plate.
• The solids form a filter cake and remain in the frame.
• The thickness of the cake is half of the frame thickness because, on each side of the frame, filtration occurs.
• Thus, two filter cakes are formed, which meet eventually in the center of the frame.
• In general, there will be an optimum thickness of filter cake for any slurry, depending on the solid content in the slurry and the resistance of the filter cake.
• The filtrate drains between the projections on the surface of the plate and escapes from the outlet.
• As filtration proceeds, the resistance of the cake increases,s and the filtration rate decreases.
• At a certain point, it is preferable to stop the process rather than continue at very low flow rates.
• The press is emptied and the cycle is restarted.

2. Washing operation:

• If it is necessary to wash the filter cake, the ordinary plate and frame press is unsatisfactory. Two cakes are built up in the frame meeting eventually in the middle.
• This means that flow is brought virtually to a standstill.
• Hence, water washing using the channels of the filtrate is very inefficient, if not impossible. A modification of the plate and frame press is used.
• For this purpose, an additional channel is included. These wash plates are identified by three dots.
• In half the wash plate there is a connection from the wash water channel to the surface of the plate

The sequence of arrangement of plates and frames can be represented by dots as 1.2.3.2.1.2.3.2.1.23.2.1 and so on (between 1 and 1,23.2 must be arranged). Such an arrangement for the operations of filtration and water washing, respectively.

The steps are as follows:

1. Filtration proceeds in the ordinary way until the frames are filled with cake.
2. To wash the filter cake, the outlets of the washing plates (three dots) are closed.
3. Wash water is pumped into the washing channel. The water enters through the inlets on to the surface of the washing (three dots) plates.
4. Water passes through the filter cloth and enters the frame (two dots) which contains the cake. Then water washes the cake, passes through the filter cloth, and enters the plate (one dot) down the surface.
5. Finally, washed water escapes through the outlet of that plate.

Thus with the help of special washing plates, the wash-water can flow over the entire surface of the washing (three dots) plate, so that the flow resistance of the cake is equal to all points. Hence, the entire cake is washed with equal efficiency.

It should be noted that water washing is efficient only if the frames are full of filter cake. If the solids do not fill the frame, the wash water causes the cake to break (on the washing plate side of the frame) then washing will be less effective. Hence, it is essential to allow the frames to become filled with the cake. This helps not only in emptying the frames but also helps in washing the cake correctly.

3. Special provisions:

• Any possible contamination can be observed by passing the filtrate through a glass tube or sight glass from the outlet on each plate.
• This permits the inspection of the quality of the filtrate. The filtrate goes through the control valve to an outlet channel.
• The filtration process from each plate can be seen. In the event of a broken cloth, the faulty plate can be isolated and filtration can be continued with one plate less.

Plate And Frame Filter Press Uses:

• Filter sheets composed of asbestos and cellulose are capable of retaining bacteria so that sterile filtrate can be obtained, provided that the whole filter press and filter medium have been previously sterilized.
• Usually, steam is passed through the assembled unit for sterilization.
• Examples include collection of precipitated antitoxin, removal of precipitated proteins from insulin liquors, and removal of cell broth from the fermentation medium.
• Heating/cooling coils are incorporated in the press to make it suitable for the filtration of viscous liquids.

Plate And Frame Filter Press Advantages:

1. Construction of filter press is very simple and a variety of materials can be used.
   • Cast iron for handling common substances.
   • Bronze for smaller units
   • Stainless steel is used thereby contamination can be avoided.
   • Hard rubber or plastics where metal must be avoided.
   • Wood for lightness though it must be kept wet.
2. It provides a large filtering area in a relatively small floor space. It is versatile, the capacity being variable according to the thickness of frames and the number used. Surface area can be increased by employing chambers up to 60.
3. The sturdy construction permits the use of considerable pressure difference. About 2000 kilopascals can’ be normally used.
4. Efficient washing of the cake is possible.
5. Operation and maintenance are straightforward because there are no moving parts, and filter cloths are easily renewable. Since all joints are external, a plate can be disconnected if any leaks are visible. Thus contamination of the filtrate can be avoided.
6. It produces dry cake in the form of a slab.

Plate And Frame Filter Press Disadvantages:

• It is a batch filter so there is a good deal of ‘down-time’, which is non-productive.
• The filter press is an expensive filter. The emptying time, the labor involved, and the wear and tear of the cloth result in high costs.
• The cake is difficult to remove.
• The filter press is used for slurries containing less than 5% solids. So high costs make it imperative that this filter press is used for expensive materials.
• Examples include the collection of precipitated antitoxin and the removal of precipitated proteins from insulin liquors.

Filter Leaf

Filter leaf is the device that is used in the filtration of the solids containing the suspensions and is involved in the separation of the solids from the liquids. They are applied for polishing slurries with a very low solids content of 1 – 5% or for cake filtration with a solid concentration of 20 – 25%.

Leaf Filters are also very well suited for handling flammable, toxic, and corrosive materials since they are autoclaved and designed for hazardous environments when high pressure and safe operation are required.

The largest Leaf Filters in horizontal vessels have a filtration area of 300 m2 and vertical vessels 100 m2 both designed for an operating pressure of 6 bar.

Selection criteria:

• Leaf Filters are best selected in the following instances:
• When minimum floor space for large filtration areas is required.
• When the liquids are volatile and may not be subjected to vacuum
• When there is a risk of environmental hazard from toxic, flammable or volatile cakes specially secured discharge mechanisms may be incorporated.
• When high filtrate clarity is required for polishing applications.
• When handling saturated brines that require elevated temperatures the tank may be steam jacketed.

When the cake may be discharged either dry or as a thickened slurry, they should be selected with care:

• When the cake is thick and heavy and the pressure is not sufficient to hold it on the leaf.
• When coarse mesh screens are used the filtration step must be preceded with a precoat to retain cakes with fine particles.
• Precoating with a thin layer of diatomite or perlite is not a simple operation and should be avoided whenever possible.

Filter leaf Principle:

The principle involved in this type of filtration is the surface mechanism which acts as a sieve or strainer. A vacuum or pressure is applied to increase the rate of filtration.

Filter leaf Construction:

The Leaves:

• The slurry is pumped under pressure into a vessel that is fitted with a stack of vertical leaves that serve as filter elements. Each leaf has a centrally located neck at its bottom which is inserted into a manifold that collects the filtrate.
• The leaf is constructed with ribs on both sides to allow free flow of filtrate towards the neck and is covered with coarse mesh screens that support the finer woven metal screens or filter cloth that retain the cake.
• The space between the leaves may vary from 30 – 100 mm depending on the cake formation properties and the ability of the vacuum to hold a thick and heavy cake to the vertical leaf surface.
• The space is set by the filtrate necks of the leaves at the bottom end and
  with spacers at the top-end brackets.
• For fast filtering slurries the space may be doubled by removing every second plate so consequently the cake space doubles but the filtration area is cut in half, the leaves involve in the filter leaf.

The Vessels:

1. There are two types of vessel configuration:
2. Vertical vessels
3. Horizontal vessels
4. In most of the fine chemicals processes the leaves are fitted into vertical vessels whilst horizontal vessels are used in the heavier process industries such as the preparation of sulfur in phosphoric acid plants. The leaves inside horizontal tanks may be positioned either along the tank axis or perpendicular to the axis.
5. To utilize the tank volume for maximum filtration area the width of the leaves is graduated so they fit to the circular contour of the tank. This also reduces the slurry heel volume that surrounds the leaves.
6. The vessels are fitted with highly secured cake discharge openings to ensure the safe sealing of the tank under pressure. The cake that accumulates on the leaves may be discharged as a wet thickened sludge or as a dry cake.
7. The head cover of vertical vessels is often pivoted so that it is swung away to allow the upward removal of the leaves in the stack. It is good practice to design a special ring that will support a leaf that is removed from the vessel.
8. Special quick-opening bolts are fitted around the cover so that tightness is secured during operation but enable easy opening when access to the stack is required.

Filter leaf Working:

The operation of a leaf filter is labor intensive and requires a complex manipulation of valves so present-day installations are in most cases fully automated.

1. Precoating:
   • The precoating stage is done only in the following cases:
   • When a clear filtrate is required immediately after the filtration cycle commences otherwise recirculation must be employed until a clear filtrate is obtained.
2.  Filtration:
   • Once the precoating stage is completed the process slurry is pumped into the filter, the forming cake is retained on the leaves and the filtrate flows to further processing.
   • When the solids are fine and slow to filter a body-aid is added to the feed slurry to enhance cake permeability.
   • However, it should be kept in mind that the addition of body aid. increases the solid concentration in the feed so it occupies additional volume between the leaves and increases the amount of cake for disposal.
   • Likewise, for all those applications when the cake is the product, precoat and filtered may not be used since they mix and discharge together with the cake.
3.  Heel Removal:
   • Once the filtration cycle is completed air or gas is blown into the vessel.
   • At this point, the remaining heel slurry is evacuated back to the feed tank by a special dip pipe that is located at the very bottom of the vessel so that the vessel is empty from the slurry.
4.  Cake Drying: The air then continues to pass through the cake until the captive moisture is reduced to a minimum and the cake is in practical terms considered to be dry.
5. Cake Discharge:
   • At this point the air pressure is released, the cake outlet is opened and the leaf stack is vibrated to discharge the cake. The cake outlet opening must be interlocked with a pressure sensor to avoid opening under pressure.
   • On some filters, the cloth or mesh screen may be backwashed.with water after cake discharge to dislodge and remove any cake residue that adhered to the medium.

Filter leaf Uses:

The leaf filter is satisfactory, if the solids content of the slurry is not too high about 5% that is dilute suspension.

Filter leaf Advantages:

1. The cloth or woven mesh screens that cover the leaves of horizontal tanks may be accessed easily once the stack is pulled out of the vessel.
2. This allows thorough washing of the medium with high-impact jets manually in case that the cake bridges between the leaves.
3. On vertical tanks, the head cover must be unbolted and removed to access the leaf stack.
4. Mechanically simple since there are no complex sealing glands or bearings.

Filter leaf Disadvantages:

• High headroom is required for dismantling the leaves on vertical vessels.
• Large floor space is required for discharging the cake on horizontal vessels.
• Maintenance
• The leaf. filter requires attention regularly to safety devices and automation features that accompany modern filters.
• The space of the filter should have a hoisting device and sufficient headroom to lift each leaf and move it horizontally to a location adjacent to the filter tank.
• It is recommended to have a special rig that will hold the leaf for maintenance. Space must also be allocated for the cover which may be either hinged or removed.

Filter leaf Precautions:

• The major components that require attention are:
• The filter tank must conform to an Unfired Pressure Vessel code, such as ASME, and checked periodically as required by the safety regulations.
• The pressure relief valve that is located on the top of the tank must be checked for emergency functioning.
• The “o”-rings that seal between the leaf’s neck and the filtrate collecting manifolds.
• The large diameter caulking gasket of the dished top head cover. The ends must be cut in an angle to ensure a perfect seal.
• The hinged head cover locking bolts.
• The cleanliness of the filtrate sight glass that is monitored on-line or visually enables inspection of the filtrate clarity.
• The interlock that disables opening the cake discharge when the vessel is still under pressure.
• The maintenance hoist above the filter must pull out the leaves vertically so that they will not hit the tank wall.
• The condition of the filter medium, cloth or mesh screen, must be done periodically to ensure that they are not damaged.
• The vent on top of the head must be checked for free evacuation of air.
• The filter must not be overfilled with cake since this causes the leaves to bend so they must be checked periodically.

Rotary Drum Filter In Pharmaceutical Engineering In Pharmaceutical Engineering

A rotary vacuum filter drum consists of a drum rotating in a tub of liquid to be filtered. The technique is well suited to slurries, and liquids with a high solid content, which could clog other forms of filter. The drum is pre-coated with a filter aid, typically of diatomaceous earth (DE) or Perlite.

 Rotary Drum Filter Principle:

Rotary drum filters work on the principle or function of filtering the slurry through sieve-like mechanism on a rotating drum surface under the condition of the vacuum. In addition compression drying (using hot air) and removing the filter cake (using a knife) are possible.

 Rotary Drum Filter Construction:

The construction of a rotary drum filter consists of a metal cylinder mounted horizontally. The drum may be up to 3 meters in diameter and 3.5 meters in length and give a surface area, of the 20-meter square. The curved surface is a perforated plate, which supports a filter cloth.

The drum is radially partitioned dividing the annular space into separate compartments. Each of it is connected by an internal pipe to the center of the drum through a rotating valve. Various designs available are belt discharge, scraper discharge, roll discharge, string discharge, and precoat discharge.

 Rotary Drum Filter Working:

After pre-coat has been applied, the liquid to be filtered is sent to the tub below the drum. The drum rotates through the liquid and the vacuum sucks liquid and solids onto the drum pre-coat surface, the liquid portion is “sucked” by the vacuum through the filter media to the internal portion of the drum, and the filtrate is pumped away. The solids adhere to the outside of the drum, which then passes a knife, cutting off the solids and a small portion of the filter media to reveal a fresh media surface that will enter the liquid as the drum rotates. The knife advances automatically as the surface is removed.

Rotary Drum Filter Uses:

• It is a continuous operation and is utilized to filter slurries containing a high proportion of solids up to 15 to 30 percent.
• It is used to extract the penicillin from the mycelium or cell mass by the drum filters.
• These are used for collecting calcium carbonate, starch, and magnesium carbonate.
• A drum filter is a large and typically used in industrial applications to filter liquids carrying high concentrations of suspended solids.
• Perforated drum filters are often used in water treatment plants that remove large amounts of fine sediment from water.
• They can also be used to remove wastewater
  from suspended slurry products.

Rotary Drum Filter Advantages:

• The rotary vacuum drum filter is a continuous and automatic operation, so the operating cost is low.
• The variation of the drum speed rotating can be used to control the cake thickness.
• The process can be easily modified (pre-coating filter process).
• Can produce relatively clean product by adding a showering device.

 Rotary Drum Filter Disadvantages:

• Due to the structure, the pressure difference is limited up to 1 bar.
• Besides the drum, other accessories, for example, agitators and vacuum pump are required.
• The discharge cake contains residual moisture.
• High energy consumption by vacuum

Meta Filters In Pharmaceutical Engineering

Meta filters are the filters that are used to separate very fine-sized particles from the liquid or solid suspensions. It consists of a series of metal rings which are made of stainless steel and drainage grooves.

Meta Filters Principle:

Meta filter functions as the strainer (surface filtration) for the separation of the particles. In this method metal rings contain semicircular projections which are arranged as a nest to form channels on the edge. These channels offer resistance to the flow of solids. The clear liquid is collected into a receiver from the top.

Meta Filters Construction:

It consists of a large number of metal rings packed on a fluted rod. The groove on the surface of the rod provides a channel for the discharge of the filtrate. The rings are made of stainless steel having an internal diameter of about 15 mm and outside diameter of about 22 mm, thickness is about 0.8 mm.

The plate contains several semicircular projections. When the rings are packed on the rod channels are formed in between the plates that are tapered from about 250 mm down to 25 mm. One or more of these packs are mounted in a vessel. The slurry to be filtered is pumped under pressure or a vacuum may also be used. The cake formed can be removed from the outside edge by back flushing of water or by a scraping blade.

Meta Filters Working:

In meta filters, filters are placed in a vessel and may be operated by pumping the slurry under pressure or occasionally by the applications of reduced pressure to the outlet side. The slurry passes through the channels formed on the edge between the rings.

The clear liquid rises and is collected from the outlet into the receiver. Meta filter functions as a strainer. For the separation of the fine particles, a bed of suitable materials such as kieselguhr is first built up. The pack of rings serves essentially as a base on which the true filter medium is supported.

Meta Filters Uses:

• Meta filters are used for the clarification of syrups
• Filtration of the injection solutions.
• Clarification of the insulin liquors.
• Filtration of the viscous liquids can be achieved by applying pressure.

Meta Filters Advantages:

• Very strong, so high pressure can be used, with no danger of bursting the filter medium.
• No filter medium is required,: so running cost is low.
• Meta filter can be made of corrosion-resistant material.
• It is useful for filtering coarse particles. If a filter bed is prepared and then filtration is carried out finer particles can also be filtered.
• Removal of the cake is effectively carried out by back-flushing with water. In automatic cleaning devices, a scrapping bale cleans the outer edge.

Meta Filters Disadvantage:

It is used for low solid content.

Membrane Filters In Pharmaceutical Engineering

A membrane is a thin layer of semi-permeable material that separates substances when a driving force is applied across the membrane. Membrane processes are increasingly used for the removal of bacteria, micro-organisms, particulates, and natural organic material, which can impart color, taste, and odors to water and react with disinfectants to form disinfection by-products.

Membrane Filters Principle:

Membrane filters act just like a sieve and retain the particulate matter along with micro-organisms according to their sizes.

Membrane Filters Construction:

These are plastic membranes based on cellulose acetate, cellulose nitrate, or mixed cellulose esters with pore sizes in the micron or submicron range.  They are very thin (about 120 microns thick) and must be handled carefully. They act like a sieves trapping particulate matter on their surface.

• Several grades of filters are available with pore sizes ranging from 0.010 ± 0.002 microns to 5.0 ± 1.2 microns.
• Type codes VF and SM are given by Millipore Filter Corp. For these two extreme ranges respectively.
• Filters with pore sizes from 0.010 to 0.10 microns can remove virus particles from water or air. Filters with pore sizes from 0.30 to 0.65 microns are employed for removing bacteria.
• Filters with the larger pore sizes, viz. 0.8, 1.2, and 3.0 to 5.0 microns are employed, for example, in aerosol, radioactivity, and particle sizing applications.
• During use membrane filters are supported on a rigid base of perforated metal, plastic or coarse sintered glass as in the case of fibrous pad filters.
• If the solution to be filtered contains a considerable quantity of suspended matter, preliminary filtration through a suitable depth filter avoids clogging of the membrane filter during sterile filtration.
• They are brittle when dry and can be stored indefinitely in the dry state but are fairly tough when wet.

Membrane Filters Uses:

• It is used for sterilization of solutions containing heat-sensitive materials.
• Membrane filters fitted in disc-containing growth media can be used to grow micro¬ organisms.

Membrane Filters Advantages:

• No bacterial growth through the filter takes place during prolonged filtration.
• They are disposable and hence no cross-contamination takes place.
• Adsorption is negligible they yield no fibres or alkali into the filtrate. The filtration rate is rapid.

Membrane Filters Disadvantages:

• They may clog though rarely.
• Ordinary types are less resistant to solvents like chloroform.

Cartridge Filter In Pharmaceutical Engineering

Cartridge filters are defined as fabric or polymer-based filters designed primarily to remove particulate material from fluids. Cartridge filters use a variety of media to remove contaminants, depending on your application.

• The filter media in our cartridge filters encompass a wide range from sand, anthracite, and quartz to conditioned media for iron and manganese removal, and activated carbon.
• Cartridge filters range in style from particulate and high-purity water cartridge filters, to activated carbon filters, vent cartridge filters, and replacement cartridge filters for laboratory usage.
• Cartridge filters have a filtration range from 0.1 up to 500 microns.
• They are manufactured by affixing the fabric or polymer to a central core and they are usually rigid or semi-rigid. Cartridge filters are disposable and easily replaceable.

Cartridge Filter Principle:

A cartridge filter is a thin porous membrane in which the pre-filter and membrane filter are combined into a single unit. The filtration action is mainly sieve-like and the particles are retained on the surface.

The cartridge filter systems are basically of two styles:

1. Smaller systems usually use a single-wound cartridge.
2. Larger systems usually consist of multiple cartridge filters.

Smaller cartridge filter systems such as those used in a home filtering system typically are constructed from some type of plastic or stainless steel. The body of the vessel usually is made of clear plastic (or stainless steel).

The lid usually contains the outlet ports, inlet ports, and pressure relief valve. Taps or ports for pressure gauges may or may not be contained in a smaller cartridge filter system. Larger cartridge filter systems can use either pleated or wound filters and usually use multiple filters in a single housing.

Cartridge Filter System:

• Single Filter System: A single filter system would likely be somewhat rare in a water treatment application. A single filter system would only be applicable for extremely small systems with an extremely high-quality source of water. Home water filter systems are usually single filter systems.
• Prefilter-Post Filter System: It is configured so that the feed water initially passes through a filter with a relatively large pore size and then is filtered through the finer post or final filter.
• Multiple Filter System: A pre-filter-post filter configuration is an extension of the multiple filtration system. Rather than it is having a pre-filter and a post-filter, a multiple filtration system would consist of progressively finer filters plumbed in series.

Cartridge Filter Working:

The slurry is pumped into the cartridge holder. It passes through catridge filter unit by the mechanism of straining. The clear liquid passes to the center and moves up to collect through the outlet.

Cartridge Filter Uses:

• These are used in the filtration of sterile solutions.
• Filtration of beverages.
• Liquid filtration: Bulk chemicals, petrochemicals, water purification, hydraulic fluids, cosmetics/pharmaceuticals, reagent grade chemicals, paints, varnishes, semiconductors, sugars, electric utilities, paints/varnishes often used as final filtration after other filters
• Gaseous filtration: Gas dust removal in industrial, atmosphere, compressed air filtering, atmospheric dust, smoke, fumes, solid contaminants in the system.

Cartridge Filter Advantages:

• Stainless steel construction permits autoclaving for sterile operations.
• Cartridges with self-cleaning devices are advantageous.
• Rapid disassembling as well as reusing of the filter media is possible.
• They are used in line continuous filtration which reduces handling of solutions.
• It minimizes the chance of contamination.

Cartridge Filter Disadvantages:

• The cost of disposable elements offsets the labor-saving in terms of assembly and cleaning of cartridge clarifier.
• Several manufacturers provide components that are generally not interchangeable between suppliers.

Seitz Filter In Pharmaceutical Engineering

These are developed in Germany. Seitz filter consists of a pad of compressed asbestos as a filtering medium. Typical Seitz filter pads are about 2 mm thick and offer a wide range of sizes, they are effective in removing particles of size even less than one micrometer, down to well below one micrometer diameter. The finest pore size gives almost perfect filtration and retains small viruses. When these filters are used for air filtration, the effects of surface charging and electrostatic attraction have a significant influence in the removal of particles

Seitz filter Uses:

• Seitz filters are being used for filtration sterilization.
• The finest pads give almost perfect filtration of small volumes.
• Viscous solutions can also be filtered.
• These filters can be used for air filtration

Seitz filter Advantages:

• Filtration is rapid with fewer tendencies to clog.
• These are better than ceramic and Sintered glass filters for viscous solutions.
• The apparatus is very simple to handle.

Seitz filter Disadvantages:

• Seitz filters are pliable and fragile when wet they must be supported on metal discs.
• A new pad must be used for each filtration to avoid residues of previous filtration.
• Asbestos may shed loose fibers.
• Pad may absorb a sufficient amount of solution or drug

Filtration In Pharmaceutical Engineering Multiple-Choice Questions

Question 1. Which one of the following contains both filters as well as prefilter?

1. Meta filter
2. Rotary drum filter
3. Seitz filter
4. Cartridge filter
5. Answer: 1. Meta filter

Question 2. Which mechanism is involved in meta filter?

1. Cake filtration
2. Depth filtration
3. Surface filtration
4. Zig-Zag filtration

Answer:  3.  Surface filtration

Question 3. Which one of the following is not the property of filter aid?

1. Porous
2. Chemically active
3. Recoverable
4. Removes colour

Answer: 2.  Chemically active

Question 4. Which one of the filters is used for sterile filtration?

1. Meta filter
2. Rotary drum filter
3. Seitz filter
4. Cartridge filter

Answer:  3. Seitz filter

Question 5. Which one of the following gives the dry cake after filtration?

1. Membrane filter
2. Rotary drum filter
3. Seitz filter
4. Cartridge filter

Answer: 2. Rotary drum filter

Question 6. The purpose of using a filter, aid Is ______________

1. To prevent blockage of medium
2. During the filtration of viscous liquids
3. When the particle size is much smaller
4. To hasten the speed of filtration

Answer: 1. To prevent blockage of medium

Question 7. Which filter is used for clarification of, syrups?

1. Drum filter
2. Meta filter
3. Filter leaf
4. Plate and frame

Answer: 2. Meta filter

Question 8. The pores in the stainless steel plates act as channels in one of the following filters?

1. Meta filter
2. Rotary drum filter
3. Seitz filter
4. Cartridge filter

Answer: 1. Meta filter

Question 9. Which mechanism is involved in the plate and frame filter press?

1. Cake filtration
2. Depth filtration
3. Electrostatic filtration
4. Surface filtration

Answer: 4. Surface filtration

Question 10. Which one of the following is not a mechanism of filtration?

1. Entanglement
2. Impact
3. Straining
4. Impingement

Answer: 2. Impact

Heat Transfer In Pharmaceutical Engineering Introduction

Heat transfer is the process of transfer of heat from high high-temperature system to a low-temperature system. In terms of the thermodynamic system, heat transfer is the movement of heat across the boundary of the system due to the temperature difference between the system and the surroundings.

• The heat transfer can also take place within the system due to temperature differences at various points inside the system.
• The temperature difference is considered to be the ‘potential’ that causes the flow of heat and the heat itself is called as flux.
• There are three modes of heat transfer: conduction, convection and radiation.
• Some media is required for the transfer of heat by conduction and convection, but for radiation, no media is required.
• The process in which there is no transfer of heat between the system and its surroundings is called as adiabatic process.
• The wall or boundary which does not allows the flow of heat between the system and the surroundings is called an adiabatic wall and the wall that allows the flow of heat between the system and the surroundings is called a diathermic wall.

Heat Transfer In Pharmaceutical Engineering Objectives

• To reduce the heat or energy loss and make energy utilization more effective.
• Insulation, wherein across a finite temperature difference between the system and its surroundings, the person seeks to reduce the heat transfer as much as possible.
• Enhancement, wherein the converse of insulation, i.e. promotion of heat transfer is sought across a finite temperature difference.
• Temperature control, wherein the temperature of a region is required to be maintained close to a specified value, requires both insulation and enhancement to operate at various instances of the operational sequence of a device kept, in the region of interest.

Heat Transfer Applications In Pharmaceutical Engineering

• Evaporation: The liquid present in the material is evaporated with the help of heating to get a concentrated product.
  • For example: The preparation of vegetable extracts.
• Distillation: In the distillation, two liquids are separated by the application of heating. First; the liquid having less boiling point starts to evaporate and this evaporated liquid is then condensed in a separate part of the instrument and collected.
• Drying: Removal of a small amount of moisture from a product is called as drying. Drying generally involves the direct heating or supply of hot air over the material that is to be dried,
  • For example:  Drying of granules in tablet processing.
• Crystallization: The saturated solution is heated to make it supersaturated which promotes the crystallization process. Further, the saturated solution can be cooled to facilitate crystallization.
• Sterilization: For sterilization purposes, the two instruments are extensively used i.e. hot air oven and autoclave. These instruments use heat to kill microorganisms.

 Heat Transfer Mechanism In Pharmaceutical Engineering

Heat generally gets transferred from high-temperature regions to.

Low-temperature region by three mechanisms:

1. Conduction
2. Convection
3. Radiation

1. Conduction:

Conduction is the transfer through solids or stationary fluids. When you touch a hot object, the heat you feel is transferred through your skin by conduction.

Two mechanisms ” explain how heat is transferred by conduction:

1. Lattice vibration and
2. Particle collision

Conduction through solids occurs by a combination of the two mechanisms; heat is conducted through stationary fluids primarily by molecular collisions.

In solids, atoms are bound to each other by a series of bonds, analogous to springs.

• When there is a 3-temperature difference in the solid, the hot side of the solid experiences more vigorous atomic movements. The vibrations are transmitted through the springs to the cooler side of the solid.
• Eventually, they reach equilibrium, where all the atoms are vibrating with the same energy.
• Solids, especially metals, have free electrons, which are not bound to any particular atom and can freely move about the solid. The electrons on the hot side of the solid move faster than those on the cooler side.
• As the electrons undergo a series of collisions, the faster electrons give off some of their energy to the slower electrons. Eventually, through a series of random collisions, equilibrium is reached, where the electrons are moving at the same average velocity.
• Conduction through electron collision is more effective than through lattice vibration; this is why metals generally are better heat conductors than ceramic materials, which do not have many free electrons.

In fluids, conduction occurs through collisions betv/een freely moving molecules. The mechanism is identical to the electron collisions in metals.

2. Convection:

Convection uses the motion of fluids to transfer heat. In a typical convective heat transfer, a hot surface heats the surrounding fluid, which is then carried away by fluid movement such as wind.

• The warm fluid is replaced by cooler fluid, which can draw more heat away from the surface.
• Since the heated fluid is constantly replaced by cooler fluid, the rate of heat transfer is enhanced.
• Natural convection (or free convection) refers to a case where the fluid movement is created by the warm fluid itself.
• The density of fluid decreases as it is heated; thus, hot fluids are lighter than cool fluids. Warm fluids’ surrounding a hot object rise and is replaced by cooler fluid.
• The result is a circulation of air above the warm surface. Forced convection uses external means of producing fluid movement.
• Forced convection is what makes a windy, winter day feel much colder than a calm day with the same temperature.
• The heat loss from your body is increased due to the constant replenishment of cold air by the wind.
• Natural wind and fans are the two most common sources of forced convection.

3. Radiation

Radiation is a heat transfer process in which heat flows through space using electromagnetic waves.

• Radiative heat transfer occurs when the emitted radiation strikes another body and is absorbed.
• We all experience radiative heat transfer every day; solar radiation, absorbed by our skin, is why we feel warmer in the sun than in the shadow.
• The type of radiation emitted is determined largely by the temperature of the body

Heat Transfer Conduction

Heat can flow only when there is a temperature gradient, i.e. heat flows from a hot surface to a cool surface. The rate of conduction through solids can be studied easily, since it is the sole phenomenon.

The basic law of heat transfer by conduction can be written in the form of rate equation as follows:

Rate= Driving / Resistance ………………………… (1)

1.  Fourier’s Law:

• The resistance term in the heat transfer equation is given by Fourier’s law. Consider an area A of a wall thickness L.
• Let the temperature be uniform over area A on one face of the wall, and uniform but lower over area A on the opposite side, then the heat flow is at right angles to the plane of A.
• Fourier’s law states that “the rate of heat flow through a uniform material is directly proportional to the area, the temperature drop, and inversely proportional to the length of the path of the flow.”
• If a small section of thickness dL, parallel to the area A is taken at some intermediate point in the wall with a temperature difference of dt across such a layer, then

Fourier’s law is represented by the following equation:

dQ / dθ = -kAdt/dL ……………………… (2)

Where k is the proportionality constant. K is known as the thermal conductivity of the solid of which the wall is made up of. The minus sign is given as temperature decreases in the direction of the flow so that dc/dt is negative. If the temperature gradient Dt/dL, does not vary with time, then the rate of heat flow is constant with time and

dQ/ dθ  = Constant q = -kAdt/dL ……………………… (3)

Normally, the temperature at the two faces of the wall and not the intermediate temperature along. the path of heat transfer can be measured. The use of Fourier’s requires that the differential equation is integrated over the path from L = 0 to L = Total length.

Rearranging the above equation,

qdL/ A= -kdt  …………………………………… (4)

If t is a higher temperature

……………………………………… (5)

The variation of k with temperature may be taken as linear, so that km, the arithmetic mean value of k may be considered constant.

dL/ A = km (t₁ – t₂) = k_m Δt

Or q= k_m Δt/L

By comparing the above equation with the rate equation and knowing that Δt is the driving force, L / K_m A is the resistance.

Heat Transfer through a Compound Resistance in Series:

Consider a flat wall constructed of a series of layers. Let the thickness of the three layers be L₁, L₂, and L₃ respectively. The conductivity of the materials of which the layers are made be k₁, k₂, and L₃ and let the area of the compound wall at a plane perpendicular to the plane of illustration be A and the temperature drops across the 3 layers be Δt₁, Δt₂, Δt₃ respectively.

Let Δt be the temperature drop across the 3 layers then

Δt = Δt₁ + Δt₂ + Δt₃

The equation (6) can be modified for At as

Where, R = R₁,  R₂, R₃, are resistances, the equation can be written as

Rate = Driving force / Resistance

Heat Flow through a Cylinder:

Consider a cylinder with internal radius ri, outside radius r₂, and length of the cylinder N. The mean thermal conductivity of the material of the cylinder is km. The temperature on the inside surface is ti and that of the outside is t₂.

t₁> t₂ therefore heat is flowing from inside to outside. To calculate heat flow for the cylinder let us consider a very thin cylinder, concentric with a main cylinder of radius r, where r₁ > r > r₂, thickness of the wall is dr, dr < < < r, so that lines of heat flow may be considered parallel

Now,

Heat Transfer Convection

When fluid flow is such that the Reynolds number exceeds a certain value, the character of the flow changes from viscous to turbulent; even in turbulent flow there is at the boundary a residual film that persists in viscous flow.

The turbulence may be caused by a stirrer or agitation by pumping (forced convection) or by the natural convection currents set up when the body of fluid is heated.

• If heat is passed through the retaining wall of the fluid, the film is of great importance in determining the rate of heat transfer.
• All the heat reaching the bulk of the fluid must pass through this film by conduction.
• The thermal conductivity of the fluids is low.
• Although the film is by a stirrer or agitation by pumping (forced convection) or by the natural convection currents set up when the body of fluid is heated.
• If heat is passing through the retaining wall of the fluid, the film is of great importance in determining the rate of heat transfer, All the heat reaching the bulk of the fluid must pass through this film by conduction.
• Thermal conductivities of the fluids are low. Although the film is low, the resistances offered by the films are high.
• Beyond the film, the turbulence brings about rapid equalization of temperature.

Temperature Gradients in Forced Convection:

The temperature distribution across a column of fluid, which is in forced convection and simultaneously heated or cooled, is related to velocity distribution across the column

• Represents temperature gradients in the case where heat is flowing from a hot fluid through a metal wall into a cold fluid.
• The dotted lines F₁ F₁ and F₂ F₂ on each side of the metal wall represent the boundaries of the films in viscous flow.
• All parts of the fluid to the right of F₁F₁ and the left of F₂ F₂ are in turbulent flow.
• The temperature gradient from the bulk of the hot fluid to the metal wall is represented by the curved line ta t_bt_c.
• Temperature ta is the maximum temperature in the hot fluid.
• Temperature tb is the temperature at the boundary between turbulent and viscous regiments and tc is the temperature at the actual interface between fluid and solid. The significance of the line t_dt_et_f is similar

The temperature of the fluid is neither the maximum temperature tn nor minimum temperature tb at the outside surface of the film but rather the average temperature of the fluid such as that after thorough mixing of fluid and taking its temperature.

• This average temperature ti will be somewhat less than t₃ and is represented by dotted line Mm and the same is true with a cold fluid whose average temperature is t₂ and marked by dotted line Nn.
• If the fluid is not too viscous, or the pipe is not too large, these average temperatures are the ones that will be given when the thermometer is inserted into the pipe.
• To determine the actual course of the curve t_a t_bt_c careful measurement with fine thermocouples is necessary.
• Temperature gradient tc td is caused by the flow of heat purely by conduction through a material whose thermal conductivity is known.

Surface Coefficients: 

The indicates that the thermal resistances in the two fluids are quite complicated.

An indirect method used for their calculation involves the use of surface coefficients. In the suppose that q is the amount of heat flowing from hot fluid to cold fluid, then q must pass from hot fluid to metal wall and the same q must pass from wall to cold fluid. Let the area of the metal wall perpendicular to the direction of heat flow on the hot side be A₁. The area on the cold side is A₂ and the average area is Am.

The surface co-efficient on the hot side is defined by relation:

h1= q / A₁(t₁-t₂)

= q / A₁ (t₁-t₂)

Compared with equation q = kA Δt/L

h₁ is analogous with k/L and 1/h₁A₁ is thermal resistance.

The thermal resistance is due to the combined effect of viscous film HH and turbulent core.

This resistance is caused by the difference in temperature t_a – t_b

In the same way, thermal resistance on the cold side h₂ may be given by

h₂ =  q/ A₂ (t_d-t₂)

This can be considered as 3 resistances in series, first resistance on the hot side 1/h₁A₁ second thermal resistance of the metal wall L/ kA_m, and third resistance on the cold side 1/h₂A₂. If this is substituted in the equation

Rate of heat transfer = Over heat transfer coefficient × Area of heating surface ×  Temperature drop

If either of two areas, A_m or A₂, had been chosen, the coefficient based on these areas would be derived and denoted by U_m and U₂

Heat Transfer from Condensing Vapours:

When hot vapors come in contact with the surface of a lower temperature, they undergo condensation.

There are two ways by which condensation may occur:

1. Film-wise condensation
2. Dropwise condensation

In film condensation, condensate wets the surface by forming a continuous film over the surface. It generally occurs on clean, uncontaminated surfaces. The latent heat liberated during condensation is transferred. through the film to the surface by conduction. The thermal gradient in the film acts as resistance to heat transfer.

• In drop-wise condensation, vapor condenses into small droplets of various sizes which may grow in size or coalesce with neighboring droplets and eventually roll off the surface. under the influence of gravity.
• During drop-wise condensation, a large portion of the area of the condensing surface remains directly exposed to vapor. Therefore the rate of heat transfer is 5 to 10 times more than film-wise condensation.
• Therefore drop drop-wise condensation is preferred over film-wise condensation. But drop-wise condensation is difficult to achieve and maintain for a long time and hence in industrial equipment film film-wise condensation occurs.
• If the condensing vapor contains some noncondensable gases like air, the heat transfer coefficient decreases significantly. This is because after the condensation of vapor non-condensable gas is left at the surface which acts as a thermal resistance to the condensation process

Heat Transfer By Radiation In Pharmaceutical Engineering

Radiation may be considered as energy streaming through space at the speed of light. All substances at a temperature above absolute zero emit radiation that is independent of external agencies. This is called thermal radiation. Material may emit radiation when treated with external agencies like electron bombardment, electric discharge, etc.

• Such type of radiation does not come under thermal radiation. Radiation as such is not heat and when transformed into heat absorption it is no longer radiation.
• If the radiation is passing through space, it is not transformed into heat or any other form of energy or it is directed from its path.
• But if matter appears in its path the radiation is transmitted, reflected, and absorbed. Only the absorbed energy is quantitatively converted into heat.
• In the majority of cases, the radiant energy emitted is continuous and distributed over all wavelengths from 0 to ∞, in principle, any wavelength in the range 0 to oo be convertible heat on absorption by matter. The portion of the electromagnetic spectrum that is of importance in heat flow lies in the wavelength of 0.8 to 25 μ.
• The amount and kind of thermal energy radiated by a surface increases rapidly with temperature. When a ray of thermal radiation strikes the surface of a body a portion of incident energy may be reflected, may be absorbed, and transmitted through the body.
• The fraction of incident energy falling on a surface which is reflected by it is called reflectivity (ρ).
• The fraction of incident energy falling on a surface that is absorbed [absorptivity (α)].
• The fraction of incident energy falling on a body that is transmitted i.e. transmissivity (x).

α + τ+ ρ = 1

A body that absorbs all incident radiation falling on it is black.

α  = I and  τ + ρ  = 0.

A black body is a theoretical substance to which all discussions refer. A black body is defined as a body that radiates the maximum possible amount of energy at a given temperature. No actual physical substance is a perfect black body.

1.  Laws of Radiationl:

Kirchoff’s Law:

The emissive power of the body £ is the radiant energy emitted from the unit area in unit time. Kirchoff’s law establishes a relationship between the emissive powers of a surface to its absorptivity.

• If a small body is placed inside a large evacuated enclosure with wall temperature T, the heat will be exchanged between the body and the enclosure until equilibrium is established i.e. Enclosure wall and body will have the same temperature.
• The body will emit as much energy as it absorbs. Now, if e is the emissive power of the body, a is absorptivity and G is the rate at which energy falls from the wall of the body,

The energy balance can be given as:

G α = E

G = E/α

The rate of energy fall is the function of temperature T and the geometrical arrangement of both surfaces. But if the body is very small as compared to the enclosure and its effect upon the irradiation field of the enclosure is negligible then G remains constant at temperature.

This is stated by Kirchoff’s law that the ratio of emissive power to absorptivity is the same for all bodies in thermal equilibrium.

E₁/α₁ = E₂/α₁₂

Where E₁ and E₂ are emissive powers of the two bodies and α₁  and α₂ are absorptivities of the two bodies.

For a black body α = 1

E_b/1 = E/α

A = E/E_b

As the black body is a perfect radiator, it is used for the comparison of emissive powers. The ratio of emissive powers of surface to the emissive power of a black body Eb is known as emissivity

ε = E/E_b

The emissivity of the body = Absorptivity at thermal equilibrium

Although the emissivity of the surface varies with the wavelength for certain materials, it is a constant fraction of the emissive power of perfectly black body Eb therefore E/Eb is constant. Such materials that have constant emissivity are known as grey bodies. For grey bodies, the two bodies don’t have to be in thermal equilibrium to apply Kirchoff’s law.

Stefan-Boltzmann Law:

Stefan-Boltzmann law states that the emissive power of the black body is proportional to the fourth power of absolute temperature.

q = bAT⁴

Where

q = Energy radiated per hour

A = Area of radiating surface

T = Absolute temperature of radiating surface

b = Constant

No actual body radiates as much as a black body. It can be expressed as,

q =  ε bAT⁴

Where e is the emissivity of the body.

Consider a small black body of area A and temperature T₂, completely surrounded by a hotter black body of temperature T₁. The net amount of heat transferred from the hotter body to the colder body is, therefore, the algebraic sum of radiation from the two bodies

So Stefan Boltzmann’s law is written as:

q = bAT⁴₁ – T⁴₁

Heat Exchangers And Heat Interchangers In Pharmaceutical Engineering

Most pharmaceutical and chemical industries use a variety of heat transfer equipment.

The heating media may be hot fluid or condensed steam.

1. Heat exchangers: Heat exchangers are devices used for transferring heat from one fluid (gas or steam) to another fluid (liquid) through a metal wall.
2. Heat interchangers: Heat interchangers are the devices used for transferring heat from one liquid to another or from one gas to another through a metal wall.

1. Heat Exchangers:

Classification of Heat Exchangers by Flow Configuration:

There are four basic flow configurations

1. Counter Flow.
2. Concurrent Flow.
3. Cross Flow.
4. Hybrids such as Cross Counterflow and Multi-Pass Flow.

Classification based on construction:

• Shell and Tube Heat Exchanger.
• Plate Heat Exchanger.
• Regenerative Heat Exchanger.
• Adiabatic Wheel Heat Exchanger.

Equipments:

1. Shell and tube heat exchanger (tubular heater):

The shell and tube heat exchanger is made up of a bundle of parallel heat exchanger tubes held in place with tube sheets and placed into a shell.

• The heat exchange always takes place between two fluids through the heat exchanger tube wall.
• There are quite a variety of flow options for shell and tube heat exchangers. In all of the configurations for shell and tube heat exchangers, one fluid passes through the tubes (the tube side fluid) and the other passes through the shell (the shell side fluid).
• The choice of shell and tube heat exchanger configuration affects the overall heat transfer coefficient and thus also affects the rate of heat transfer and the heat exchanger tube surface area needed.
• Important components of a shell and tube heat exchanger in addition to tubes (can be U-tube or straight tube) and shell are the tube sheets, baffles, end channels for the tube side fluid, and inlet and outlet nozzles for both the shell side fluid and the tube side fluid.
• The tube sheets serve to hold the tubes in place in a “tube bundle” and also can serve as baffles to create turbulence and a more consistent residence time for the shell side fluid.
• The end channels distribute the tube-side fluid and create either a transition to the outlet nozzle or a means to send the tube-side fluid back to the other end of the heat exchanger.

A straight-tube heat exchanger is easier to clean than a U-tube heat exchanger, so it is better for a tube-side fluid that tends to foul the tube, causing a need for regular cleaning. The U-tube heat exchanger works well if the two fluids have greatly different thermal expansion characteristics because it can allow the tube and the shell to expand or contract independently.

Number of passes:

The number of passes refers to the tube side fluid. The shell and tube heat exchanger is commonly made in single-pass, two-pass, and four-pass configurations, although custom multipass heat exchangers with yet another number of passes are also available

Tubular Heater Advantage:

A large heating surface can be packed in a small area.

Tubular heater Disadvantages:

• The velocity of liquid flowing in these tubes is low.
• The expansion of tubes takes place due to differences in temperatures. This may lead to loosening of the tube sheets.

2. Floating head heater:

The expansion of the tubes due to temperature differences is the problem of tubular heaters. To overcome this problem some modifications have been done in the design of it. It is called a floating head heater. To make easy removal of the tube bundles possible and to allow for considerable expansion of the tubes, a floating head exchanger is used. In this, exchanger tubes are fixed at both the ends of the floating and stationary tube sheets. The stationary tube sheet is clamped between shells

The floating tube sheet is clamped between the floating head and a clamp ring. The ring which is split in half to permit dismantling is placed at the back of the tube sheet and shows the details of a split ring assembly. The floating tube sheet is kept slightly smaller in diameter than the inside diameter of the shell to withdraw the entire tube bundle from the channel end. The channel is provided with an inlet and outlet connection for tube-side fluid. The shell is closed by a shell cover or bonnet on a floating head side.

The shell cover at the floating head end is larger than the other end to enable the tubes to be placed as near as possible to the edge of the fixed tube sheet. The tube sheet along with the floating head is free to move and take the differential thermal expansion between the shell and the tube bundle.

Floating head heater Types:

1.  Internal floating head
   • With clamp ring
   • Without clamp ring
2.  External floating head

Floating head heater Applications:

• Used as steam superheaters
• Phase change units (Reboilers)

Floating head heater Advantages:

• The tubes of the exchanger are removable for inspection and mechanical cleaning of the outside of the tubes.
• It eliminates differential expansion problems.
• The heat exchanger can be operated under high temperature and high pressure, the average temperature is less than or equal to 450°C, and the pressure is less than or equal to 6.4 MPa.

2. Heat Interchangers

The heating medium is a hot liquid which heats a cold liquid. Film coefficients of both inside and outside the tube are nearly of the same magnitude and the value of the overall heat transfer coefficient is nearer to the smaller of the two coefficients.

• Film coefficients can be enhanced by increasing the velocity of the flow of both fluids. It is difficult to increase the velocity of fluid outside the tubes.
• However, the surface area of contact can be increased by introducing baffles. Baffles consist of circular discs of sheet metal with one side cut away.
• They are perforated to receive the tubes. Baffles are supported by one or more guide rods, which are fastened between tubes by sheets.
• They are placed outside the tube. They increase the surface area of contact for liquid outside the tube and. make the liquid flow more or less at right angles to a tube which creates more turbulence.

1. Liquid to liquid heat interchanger:

The construction of a liquid-to-liquid heat interchanger is shown in the figure. Usually, tube sheets and baffles are assembled first then tubes are installed.

• Baffles are arranged in the proper place by using short sections of the same tube.
• The ends of the tubes are expanded into tube sheets.
• The entire assembly is enclosed in a shell. Shell has a provision for introducing a heating medium i.e., hot fluid. On each side of the tubes, two distribution chambers are provided. The left side chamber contains an inlet for fluid to be heated.
• The outlet for heated fluid is provided at the center of the right-side distribution chamber.
• Hot fluid is pumped from the left side top of the shell. Fluid flows outside the tubes and moves down to the bottom. Then it changes in direction and rises.
• This is continued till it leaves the heater. Baffles lengthen the path and increase the cross-section of the path.
• Liquid to be heated is pumped through the inlet provided on the left side distribution chamber. It flows through the tube and heated liquid is collected through the tube in a single pass.
• Heated liquid is collected on the right side distribution chamber.

2. Double pipe heat interchangers:

Where conditions are such that the relation between the volume of liquid inside tubes, the velocity desired and the size of the tube desired results in only a few tubes per pass, the simplest construction is the double pipe heat interchanger.

• One liquid flows through the inside of the pipe and the second liquid flows through the annular space between the pipes.
• These are primarily used for low flow rates, high-temperature drops, and high-pressure applications because of their relatively small pipe diameters.
• Outer pipe size varies from 2 to 4 inches with inner tubes varying from 3/4 to 2.5 inches in size.
• Some have longitudinal fins on the outside of the inner tube. Standard double-pipe sections with removable tubes and with provision for differential expansion between outer and inner tubes are commercially available.
• Counter-current flow in these interchangers is advantageous when very close temperature approaches are required.
• Multiple double pipe sections are also available with 8 and 16-inch outer pipe sections. Double pipe exchangers are also available in glass and impervious graphite constructions.

Heat Transfer In Pharmaceutical Engineering Multiple-Choice Questions

Question 1. When heat is transferred by molecular collision, it is referred to as heat transfer by

1. Conduction
2. Convection
3. Radiation
4. Scattering

Answer: 1. Conduction

Question 2. When heat is transferred from a hot body to a cold body in a straight line, without affecting the intervening medium, it is referred to as heat transfer.

1. Conduction
2. Convection
3. Radiation
4. Conduction and convection

Answer: 3. Radiation

Question 3. When heat is transferred from one particle of a hot body to another by the actual motion of the heated particles, it is referred to as heat transfer by _____________

1. Conduction
2. Convection
3. Radiation
4. Conduction and convection

Answer: 1. Conduction

Question 4. In radiative heat transfer, a gray surface is one _____________

1. Which appears gray to the eye.
2. Whose emissivity is independent of wavelength.
3. Which has reflectivity equal to zero.
4. Which appears equally bright from all directions.

Answer: 2. Whose emissivity is independent of wavelength.

Question 5. Heat transfer takes place according to _____________

1. First Law of Thermodynamics.
2. Second Law of Thermodynamics.
3. Third Law of Thermodynamics.
4. Zeroth Law of Thermodynamics.

Answer: 2. Second Law of Thermodynamics.

Question 6. Fourier law of heat conduction is based on the assumption that_____________ 

1. Heat flow through a solid is one-dimensional.
2. Heat flow is in a steady state.
3. Both (1) and (2).
4. None of the options.

Answer: 3. Both (1) and (2).

Question 7. To which type of heat flow Fourier’s law is applicable?

1. Conduction
2. Convection
3. Radiation
4. Conduction and convection

Answer: 1. Conduction

Question 8. The flow of heat does not apply to_____________

1. Centrifugation
2. Crystallization
3. Drying
4. Refrigeration

Answer:  1.  Centrifugation

Question 9. Drop-wise condensation of steam is possible in one of the following conditions of the pipe?

1. Clean surface
2. Rough surface
3. Greasy surface
4. Smooth surface

Answer: 3. Greasy surface

Question 10. Which equipment causes the heat transfer by radiation?

1. Hot air oven
2. Incubator
3. Micro
4. Refrigerator

Answer: 3. Micro

Mixing In Pharmaceutical Engineering Introduction

Mixing may be defined as the process in which two or more two components in a separate or roughly mixed condition are treated in such a way so that each particle of any one ingredient lies as nearly as possible to the adjacent particles of other ingredients or components.

Mixing of gas with another gas, mixing of miscible low-viscosity liquids, and mixing of a highly soluble solid with a low-viscosity liquid to effect dissolution are relatively simple as compared to the mixing of gases with liquids, mixing of liquids of high viscosity though miscible, mixing of two immiscible liquids such as aqueous and oily solutions to form emulsions, mixing of solids with liquids when the proportion of solids is high and mixing of solids with solids, specialized equipment are required for these operations.

Mixing may involve the mixing of gases, solids, or liquids in any possible combination and ratio. In pharmacy solid-solid, solid-liquid, and liquid-liquid mixing operations are common. On a small scale, it includes speculation, trituration, tumbling, geometric dilution, etc while in industries large-scale equipment is used.

Mixing In Pharmaceutical Engineering Objectives

• To have uniformity in the different ingredients used in the formulation.
• To impart the same properties throughout the content of formulation, For example: dissolution of tablets.
• To initiate or to enhance the physical or chemical reactions For example: diffusion, dissolution, etc.
• To have the same physiological effect from all the portions of the final product.

Mixing Applications In Pharmaceutical Engineering

The applications of mixing are very wide in pharmacy. It is_ nearly impossible that any pharmaceutical product hasn’t undergone the mixing operation during its manufacturing process.

• Tablet processing: A Tablet is a blend of many excipients along with e rug. 0 or uniform distribution of these all ingredients mixing step becomes essen becomes more important if the drug is potent.
• Capsule manufacture: Before feeling the drug into capsules it needs to be mixed with other ingredients like diluents, colorants, etc.
• Semisolid dosage forms: During the production of ointments or creams the rug has to be mixed with semisolid base uniformly.
• During the manufacture of powders, dry syrup mixing is done.
• Mixing of liquids is involved in the manufacture of syrups, emulsions, suspensions

Mixing Factors Affecting

The factors which are involved in the proper mixing are generally related to the powder characteristics. These factors are mentioned below.

1. Nature of the product: The rough surface of one of the components does not induce proper mixing. The reason for this is that the active substance may enter into the pores of the other ingredient. A substance that can adsorb on the surface can decrease aggregation,
   • For example: The addition of colloidal silica to a strongly aggregating zinc oxide can make it a fine dusting powder that can be easily mixed.
2. Particle size: Variation in particle size leads to separation as the small particles move downward through the spaces between the bigger particles. As the particle size increases, flow properties also increase due to the influence of gravitational force on the size. It is easier to mix two powders having approximately the same particle size.
3. Particle shape: Ideally for proper mixing shape should be spherical. If the particles have irregular shapes they can be locked into each other which is very difficult to mix uniformly with other powders.
4. Particle charge: Some particles exert attractive forces due to electrostatic charges on them. This results in separation or segregation
5. Density of the particles: This affects the mixing as the material of high density has a natural tendency to move downwards during the motion. Demixing is accelerated when the density of smaller particles is high.

Difference Between Soup And Liquid Mixing

Fluid mixing depends on the creation of flow currents, which transport unmixed material to the mixing zone adjacent to the impeller. In heavy pastes or masses of particulate solids, there are no such currents possible.

• The power required for mixing dry solids and viscous pastes is higher than that consumed in blending liquids
• After mixing product appears truly homogenous liquid phase. In mixing pastes and powders the product often consists of two or more easily identifiable phases, each. of which may contain individual particles of considerable size.
• The study of mixing in liquids requires very less samples while the study of mixing in solids involves a large number of samples.
•  Fluid mixing equipment is termed liquid agitators. Solid mixing equipment is commonly referred to as mixers and blenders.
•  Further, the transportation movement does not cause the separation of liquids while in the case of solids, there are chances of separation during transportation. are

Mixing Mechanism In Pharmaceutical Engineering

1. Solid Mixing

The mixing of powders is often a readily reversible process. Particles change their positions during movement and they tend to separate again. Mixing of powders occurs when unidentical particles exchange their positions. There are three mechanisms have been identified which are responsible for the mixing of powders. These mechanisms are convection, diffusion, and shear. In any particular process, one or more of these three basic mechanisms may be involved. Other mechanisms such as segregation can also be involved during particle motions.

Convective mixing:

During convective mixing, masses or groups of particles transfer together from one location to another.

• During this type of mixing, a circulating flow of powder is usually caused by the rotational motion of a mixer vessel, an agitating impeller (such as a ribbon or a paddle), or gas flow.
• This circulating flow contributes mainly to a macroscopic mixing of bulk powder mixtures.
• Large portions of the total mix are moved at relatively high rates, and changes at a microscopic scale are not expected.
• Therefore, pure convection tends to be less effective, leading to a final mixture, which may still exhibit poor mixing characteristics on a fine scale.
• Convective mixing is beneficial for batch mode operations but gives unfavorable effects for continuous mode mixing.

Diffusive mixing:

• Diffusive mixing (or random wall phenomenon) is caused by the random motion of powder particles. The rate of mixing by.
• This mechanism is low compared with convective mixing, but diffusive mixing is essential for microscopic homogenization.
• Pure diffusion, when feasible, is highly effective, producing very intimate mixtures at the level of individual particles but at an exceedingly slow rate.

Shear mixing:

• In shear mixing, the forces of attraction are broken down so that each particle moves on its between regions of different compositions and parallel to their surfaces.
• In a particulate mass, the forces of attraction, are predominating which makes the layers slip over one another.
• Such types of attraction forces are predominant among the same type of particles. Shear forces reduce these attractions and reduce the amount of segregation.

2. Liquid Mixing

Mixing of liquids involves four different mechanisms i.e. bulk transport, turbulent mixing, laminar mixing, and molecular diffusion. Usually more than one of these processes < is involved in the mixing.

Bulk transport:

• The movement of a relatively large portion of the material being mixed from one location in the system to another is called bulk transport.
• A simple circulation of material in a mixer may not necessarily result in efficient mixing.
• For bulk transport to be effective it must result in a rearrangement or permutation of the various portions of the material to be mixed.

Turbulent Mixing:

• The phenomenon of turbulent mixing is a direct result of turbulent fluid flow, which is characterized by a random fluctuation of the fluid velocity at any given point within the system.
• The fluid velocity at a given instant may be expressed as the vector sum of its components in the x, y, and z directions.
• With turbulence, these directional components fluctuate randomly about their mean values, as does the velocity itself.
• In general, with turbulence, the fluid has different instantaneous velocities at different locations at the same time.

This observation is true for both, the direction and the magnitude of the velocity. If the instantaneous velocities at two points in a turbulent flow field are measured simultaneously, they show a degree of similarity provided that the points selected are not too far apart.

• Turbulent flow can be conveniently visualized as a composite of eddies of various sizes.
• An eddy is defined as a portion of fluid moving as a unit in a direction often contrary to that of the general flow.
• Large eddies tend to break up; forming eddies of smaller and smaller sizes until they are no longer distinguishable.
• The size distribution of eddies within a turbulent region is referred to as the scale of turbulence.
• It is readily apparent that such temporal and spatial velocity differences, as a result of turbulence within a body of fluid, produce a randomization of the fluid particles.
• For this reason, turbulence is a highly effective mechanism for mixing. Thus, when small eddies are predominant, the scale of turbulence is low.

Laminar mixing:

• Streamline or laminar flow is frequently encountered when highly viscous liquids are being processed.
• It can also occur if stirring is relatively gentle and may exist adjacent to stationary surfaces in vessels in which the flow is predominantly turbulent.
• When two dissimilar liquids are mixed through laminar flow, the shear that is generated stretches the interface between them.
• If the mixer employed folds the layers back upon themselves, the number of layers and hence the interfacial area between them increase exponentially with time.

 Molecular diffusion:

The primary mechanism responsible for mixing at the molecular level is diffusion resulting from the thermal motion of the molecules.

When it comes in conjunction with laminar flow, molecular diffusion tends to reduce the sharp discontinuities at the interface between the fluid layers, and if allowed to proceed for sufficient time, results in complete mixing.

The process is described quantitatively in terms of Fick’s law of diffusion:

⇒ Dm/ dt = – DA dc/dx

Where, the rate of transport of mass, dm/dt across an interface of area A is proportional to the concentration gradient, dc/dx, across the interface. The rate of intermingling is governed also by the diffusion coefficient, D, which is a function of variables including fluid viscosity and size of the diffusing molecules. The concentration gradient at the original boundary is a decreasing function of time; approaching zero as mixing approaches completion.

Equipment Used In Mixing Double Cone Blender In Pharmaceutical Engineering

Double Cone Blender Principle:

The mixing of powder in a double-cone blender occurs due to the tumbling action of the blender as well as the shearing action with the blade.

Double Cone Blender Construction:

This consists of a metal container that tapers towards both ends. It is made up of stainless steel. They are fixed on the horizontal axis in such a way that the container will have rotations around the axis. It has one port to load and unload the material. It is available in different sizes ranging from 5 kg to 200 kg or more. The speed of rotation depends upon the size of the blender as well as on the type of material that is to be mixed. The speed is kept between 30 to 100 r.p.m.

Double Cone Blender Working:

The material which is to be mixed is loaded in the blender. Generally, it is 50-60% of the total size of the blender. As the blender rotates the material un ergoes also be. fixed to motion and mixes the material thoroughly. The agitator blade can produce shearing action.

Double Cone Blender Advantages:

• As attrition is less the fragile granules can be blended.
• Available in various sizes.
• Operation is easy.
• Easy to load, unload, and clean.

Double Cone Blender Disadvantages:

• Requires high head space for installation.
• Less shear is applied. So, the fine materials and the materials with large size distribution cannot be mixed efficiently.

Mixing Twin Shell Blender

 Twin Shell Blender Principle:

The primary principle of blending in a V-Blender is diffusion. Diffusion blending is characterized by small-scale random motion of solid particles. Blender movements increase the mobility of the individual particles and thus promote diffusive blending. Diffusion blending occurs when the particles are distributed over a freshly developed interface. In the absence of segregating effects, the diffusive blending will in time lead to a high degree of homogeneity.

 Twin Shell Blender Construction:

The V-Blender is made of two hollow cylindrical shells joined at an angle of 75° to 90°. They are made up of stainless steel or transparent plastic. Average capacity ranges between 20 kg to one tonne, whereas speed is around 15 to 35 r.p.m. The blender container is mounted on the drive shaft to allow it to tumble.

Mixing Twin Shell Blender Working:

The powder to be blended is put into the blender. As the V-blender tumbles, the material continuously splits and recombines, with mixing occurring as the material free-falls randomly inside the vessel.

• The repetitive converging and diverging motion of material combined with increased frictional contact between the material and the vessel’s long, straight sides result in gentle yet homogenous blending.
• Blending efficiency is affected by the volume of the material loaded into the blender.
• The recommended fill-up volume for the V-Blender is 50 to 60% of the total blender volume.
• Discharge from the V-blender is normally through the apex port which is fitted with a discharge valve.

Mixing Twin Shell Blender Advantages:

• Particle size reduction and attrition are minimized due to the absence of any moving blades. Hence it can be used for fragile materials
• Charging and discharging of material is easy.
• The shape of the blender body results in a near complete discharge of product material, clearly an added advantage over horizontal blenders.
• The absence of shaft projection eliminates product contamination.
• V-blenders are easy to clean.

Mixing Twin Shell Blender Disadvantages:

• They require high headroom for installation and operation.
• They are not suited for blending particles of different sizes and densities which may segregate at the time of discharge.

Mixing Twin Shell Blender Uses:

V-blender designs are most often used for the dry blending of free-flowing solids. This blender is often used for pharmaceuticals, but the mixing action’s slight shear limits the blender’s use for some very soft powders or granules.

Mixing Ribbon Blender In Pharmaceutical Engineering

Ribbon Blender Principle:

The mechanism of mixing is shear. Shear is transferred to the powder bed by ribbons in a fixed shell. High shear rates are effective in breaking lumps and aggregates. Convective mixing also occurs as the powder bed is lifted and allowed to cascade to the bottom of the container.

Ribbon Blender Construction:

A ribbon blender consists of a horizontal trough containing a double helical ribbon agitator. The agitator’s shaft is positioned in the center of the trough and has welded spokes on which the helical ribbons (also known as spirals) are welded.

Since the ribbon agitator consists of a set of inner and outer helical ribbons, it is referred to as a “double” helical ribbon agitator.

• The gap between the ribbon’s outer edge and the internal wall of the container ranges from 3 to 6 mm depending on the application.
• A spray pipe for adding liquids can be mounted above the ribbons. For materials that tend to form agglomerates during mixing, high-speed choppers can be provided for the disintegration of the agglomerates The ribbon agitator is powered by a drive system comprised of a motor, gearbox, and couplings
• The agitator shaft exits the blender container at either end through the end plates bolted or welded to the container.
• The area where the shaft exits the container is provided with a sealing arrangement to ensure that material does not travel from the container to the outside and vice-versa.

Ribbon Blender Working:

The materials to be blended are loaded into the blender up to 40 and 70% of the total volume of the container. This is generally up to the level of the outer ribbon’s tip.

The ribbon agitator is designed to operate at a peripheral speed (also known as tip speed) of approximately 100 meters/minute, depending on the application and the size of the equipment.

• A spray pipe for adding liquids can be mounted above the ribbons.
• For materials that tend to form agglomerates during mixing, high-speed choppers can be provided for the disintegration of the agglomerates.
• During the blending operation, the outer ribbons of the agitator move the material from the ends to the center while the inner ribbons move the material from the center to the ends.
• Radial movement is achieved because of the rotational motion of the ribbons.
• The difference in the peripheral speed of the outer and inner ribbons results in axial movement of the material along the horizontal. axis of the blender.
• As a result of the radial and the countercurrent axial movement, homogenous blending is achieved in a short time.
• Blending is generally achieved within 15 to 20 minutes of a start-up with a 90 to 95 percent or better homogeneity.
• The particle size and its bulk density have the strongest influence on the mixing efficiency of the ribbon blender.
• Ingredients with similar particle size and bulk densities tend to mix faster as compared to ingredients with variations in their attributes.

Ribbon Blender Advantages:

• High shear can be applied using perforated baffles, which bring about the rubbing and breaking of aggregates.
• The headspace requirement is less.
• Short time of operation i.e. about 15 to 20 minutes.
• Disadvantages:
• Poor mixing abilities, because the movement of particles is two-dimensional.
• Shearing action is less than a planetary mixer.
• Dead spots are observed.

Ribbon Blender Applications:

• Blending large volumes of dry solids.
• Dry powder to wet phase mixing.
• Mixing of bulk drugs, chemicals, and cosmetic powders.
• Dry Blending of capsule formulations.
• Lubrication of dry granules in large quantities.
• Heating, cooling, and drying of materials.
• Coating solid particles with small amounts of liquids to produce formulations.

Mixing Propeller In Pharmaceutical Engineering

Propeller Principle:

The propeller mixer mainly works on the principle of shearing force.

Propeller Constructions:

It consists of a vessels and a propeller. A common arrangement for medium-scale fluid mixing is a propeller-type stirrer which may be clamped to the edge of a vessel. A propeller has angled blades, which cause the fluid to circulate in both an axial and a radial direction. The ratio of the diameter of a propeller stirrer to that of the vessel is commonly: 10 -1 : 20, and it typically operates at speeds of – 20 reps.

Propeller Working:

The propeller mixer works mainly as the fan, with a spreading plume of emanating from the mixing device. This propeller usually works at high speed which is up to 8000 rpm which gives a satisfactory flow pattern to the liquids.

During the mixing of the liquids, the air gets entrapped in the liquids or there is the formation of a vortex.

This can be avoided by making the following changes in the position of the propeller shafts.

• Offset from the center.
• Mounted at an angle.
• Enter the side of the vessel.
• Using the pull propeller.
• By the use of baffles.

Propeller Uses:

• The propeller mixer is used in mixing the liquids up to 2000 cp.
• It can mix low-viscosity emulsions.
• Liquid phase chemical reaction.
• The propeller mixer is used in mixing suspensions with particle sizes up to 0.1 to
• 0.5 mm maximum with a drying residue of 10%.

Propeller Advantages:

• Top-to-bottom mixing can be achieved in a propeller mixer.
• All sides of mixing is possible.

Propeller Disadvantages:

• The propeller mixer cost is high.
• Sensitivity in operation of vessel geometry and in location within the tank.
• The propeller mixer is not used for rapid settling suspension.

Mixing Sigma Blade Mixer In Pharmaceutical Engineering

The sigma blade mixer is a commonly used mixer for high-viscosity materials.

 Sigma blade mixer Principle:

Sigma blade mixer is designed in such a way that the viscous mass of material is pulled, sheared, compressed, kneaded, and folded by the action of the blades against the walls of the mixer trough. The extent to which this depends on the action of the blades tangential or overlapping and the ratio of the speed of rotation of the blades.

 Sigma blade mixer Construction and Working:

Material is loaded through the top of the container to typically 40 to 65 percent of the mixer’s total volumetric capacity. The rotation of the blades is through heavy-duty drive systems typically consisting of a motor, gearbox, couplings, and gears. The top speed of the Sigma mixer is generally limited to 60 revolutions per minute.

Mixing may be carried out at ambient temperature or under controlled temperature conditions. The mixer troughs can be provided with jackets for circulation of hot or cold media to maintain the required temperature conditions within the mixer.

The discharge of the material from the mixer container is either by tilting the mixer container* bottom discharge valve or through an extruder/screw located in the lower portion between the two trough compartments. The mixer may be equipped with any one of these discharge arrangements.

Sigma blade mixer Advantages:

• Less dead spots are observed.
• Ideal for mixing, and kneading of highly viscous mass and sticky products.
• These types of mixers and their variants can handle the highly. viscous materials up to as 10 million centipoises.

 Sigma blade mixer Disadvantages:

• Speed is fixed.
• High power consumption.

 Sigma blade mixer Uses:

The sigma mixer is the. best-suited mixer for pasty, sticky, and gritty slurries with high viscosities. Some of the products are made with the help of a Sigma blade mixer.

• Adhesives.
• Butyl rubber.
• Carbon pastes.
• Chemicals.
• Chewing gum.

Mixing Planetary Mixer In Pharmaceutical Engineering

A planetary mixer is a popular tool utilized in several industries ranging from food products, and medical drugs, to construction materials. This equipment is meant to mix items properly, specifically when it is necessary to form a mixture with a paste-like consistency

Planetary Mixer Principle:

In a planetary mixer, the blade tears the mass apart and shear is applied between a moving blade and a stationary wall. The mixing arm moves around its axis and also around the central axis to reach every spot of the vessel. The plates in the blade are sloped so that the powder makes an upward movement to produce a tumbling motion.

Planetary Mixer Construction:

It consists of a stationary vessel which is made up of stainless steel. The vessel is removed either by lowering it beneath the blade or raising the blade above the vessel. The mixing blade is mounted from the top of the vessel. The mixing shaft is driven by a planetary gear connected to an electric motor.

Planetary Mixer Working:

The blade is moved slowly at the initial stage for the premixing of the material and finally at increased speed for active mixing. In this way, high shear can be applied for thorough mixing. The blade and the stationary vessel provide a kneading action and shear. This is due to the narrow clearance between the blade and the wall of the vessel.

Planetary Mixer Advantages:

• The speed of rotation can be changed.
• These are easy to clean.
• It consumes less energy than Sigma blenders.
• Material discharge is easy.

Planetary Mixer Disadvantages:

• Heat is generated during operation.
• Cannot be used for continuous operation.

Planetary Mixer Uses:

• The planetary mixers are ideal for mixing creams ointments, ceramics, colors and pigments, etc.
• These are also used for the mixing of viscous pastes.
• Can be used for the wet granulation process.

Mixing Turbines In Pharmaceutical Engineering

A turbine mixer is a mechanical device that is used in mixing of different types of liquids by using different types of blades and impellers. A turbine mixer is an impeller that essentially consists of constant blade angles concerning the vertical plane, over its entire length or over finite sections having blades either vertical or a set of an angle less than 90° with the vertical. Blades may be either curved or flat.

Turbines Principle:

The turbine mixer mainly works on the principle of shearing action or force.

Turbines Construction:

Turbine mixers consist of a circular disc impeller to which several short, straight, or curved blades are attached. These mixers differ from propellers in that they are rotated at a lower speed than propellers and the ratio of the impeller and container diameter is also low. The turbine mixer produces greater shear force than propellers therefore they are used for mixing liquids of high viscosity and have a special application in the preparation of emulsions. Baffles are often used to prevent vortexes.

Turbines Working:

The mixing action is accomplished by the turbine blades which constrain and discharge the liquid. The radial flow from the impeller impinges onto the vessel walls, where it splits into two streams. These streams cause mixing in their energy. When the turbine mixers are operated at sufficiently high rotational speeds both the radial and tangential flow becomes pronounced along with the vortex formation.

The different types of blades used in these mixers are:

• Flat blades
• Disk-type flat blades
• Pitched blades
• Curved blades
• Tilted blades
• Arrowhead blades
• Pitched curved blades etc

Turbines Uses:

• The propeller mixer is used in mixing the liquids up to 2000 cp.
• It can mix low-viscosity emulsions.
•  Liquid phase chemical reaction.
• Used in mixing of suspensions with particle sizes up to 0.1 to 0.5 mm maximum with a drying residue of 10%.
• Mainly used for semisolid materials.
• It is used for mixing more viscous liquids, For example:: syrups, liquid paraffin, glycerine, etc.

Turbines Advantages:

• Fine mixing.
• Used for making true solutions.

Turbines Disadvantages:

• High cost.
• Sensitivity in operation of vessel geometry and in location within the tank.
• Not used for rapid settling suspensions.
• Not used for high-viscosity liquids.

Mixing Paddles In Pharmaceutical Engineering

Some of the liquid mixers have paddles that are used as impellers which consist of flat blades attached to a vertical shaft and rotate at a low speed of 100 r.p.m. or less. The blades have a large surface area about the container in which they are employed which helps them to rotate close to the walls of the container and effectively mix the viscous liquids or semi-solids.

A variety of paddle mixers having different shapes and sizes, depending on the nature and viscosity of the product are available for use in industries. Uses of paddle mixers: Paddles are used in the manufacture of antacid suspensions, and anti-diarrheal mixtures such as bismuth-kaolin mixture.

Paddles Advantage:

Since mixers with paddle-impellers have low speed, vortex formation is not possible with such mixers.

Paddles Disadvantage:

Mixing of the suspensions js poor, thus, baffled tanks are required.

Mixing Silverson Emulsifier In Pharmaceutical Engineering

Silverson Emulsifier Principle:

The Silverton homogenizer (emulsifier) works on the principle that the large globules in a coarse emulsion are broken into smaller globules by passing them under pressure through a narrow orifice. It produces intense shearing force and turbulence by using high-speed rotors. This turbulence causes the liquid to pass through fine interstices formed by closely placed perforated metal sheets.

Silverson Emulsifier Construction:

It consists of an emulsifier head which is covered with a fine-meshed stainless steel sieve. The emulsifier head consists of several blades that rotate at high speed to produce a powerful shearing action. The blades are rotated by using the electric motor fitted at the top.

Silverson Emulsifier Working:

The emulsifier head is placed in the vessel containing immiscible liquids, in such a way that it should get dipped into it. When the motor is started, the liquids are sucked through the fine hole, and the oil is reduced into the globules due to the rotation of the blades.

The precision-machined Silverson work head generates exceptionally high shear rates in a four-stage mixing/homogenizing process:

1. The high-speed rotation of the rotor blades within the precision machined mixing work head exerts a powerful suction, drawing liquid and solid materials upwards from the bottom of the vessel and into the center of the workhead.
2. Centrifugal force then drives the material to the periphery of the work head and subjects it to mechanical shear.
3. This is followed by intense hydraulic shear and circulated back into the mix as the product is forced through the stator screen at high velocity. Fresh material is continually drawn into the work head, progressively reducing globule or particle size and quickly resulting in a homogeneous, uniform product.
4. The materials expelled from the head are projected radially at high speed towards the sides of the mixing vessel. At the same time, fresh material is continually drawn into the work head maintaining the mixing cycle.

The effect of the horizontal (radial) expulsion and suction into the head is to set up a circulation pattern that minimizes aeration caused by the disturbance of the liquid’s surface.

Silverson Emulsifier Uses:

It is used for most products, including creams, ointments, sauces, flavoring emulsions, and pharmaceutical suspensions, this requires a globule or droplet size in the range of 2 – 5 microns. This can be achieved using a Silverson Mixer Homogenizer.

Silverson Emulsifier Advantages:

• Emulsifying and homogenizing: Emulsions (typically in the range of 0.5 to 5 microns) can be easily achieved.
• Particle size reduction: Uniformly mill both solid and semi-solid materials into either solution or fine suspension.
• Gelling and solubilizing: The high shear action of the Silverson homogenizer can rapidly disperse gums, alginates, C.M.C., carpools, etc., resulting in an agglomerate-free solution within minutes.
• Disintegration: All Silverson mixers can disintegrate matter of animal, vegetable, mineral or synthetic origin in a single operation.
•  Speed: The exceptionally rapid Silverson mixing action substantially reduces process times compared with conventional agitators and mixers, and can reduce mixing times by up to 90%.

Silverson Emulsifier Disadvantages:

There is a chance of clogging of pores of the mass.

Mixing In Pharmaceutical Engineering Multiple Choice Questions

Question 1. When a paddle is used for mixing liquids, the flow pattern of liquid is

1. Axial or tangential
2. Radial or tangential
3. Axial and tangential
4. Radial and tangential

Answer:  3. Axial and tangential

Question 2. Which type of kinetics is involved in the mixing of solids?

1. First order
2. Second order
3. Pseudo first order
4. Zero-order

Answer: 1. First order

Question 3. The mechanism of mixing in sigma bed is_______________

1. Convective mixing
2. Diffusive mixing
3. Sharing
4. Tumbling

Answer: 3. Sharing

Question 4. Which one of the following is an example of solid-liquid mixing?

1. Aluminium hydroxide gel
2. Complex elixir
3. Cod liver oil emulsion
4. Ephedrine sulphate

Answer: 1. Aluminium hydroxide gel

Question 5. Mixing of semisolid is done in

1. Double cone mixer
2. Fluidized bed mixer
3. Planetary mixer
4. Cube mixer

Answer: 3. Planetary mixer

Question 6. A planetary mixer is used for wet granulation because of its

1. Kneading action
2. Blending action
3. Shearing action
4. Agitatory action

Answer: 1. Kneading action

Question 7. Convective mixing is also called as

1. Diffusive mixing
2. Macro mixing
3. Shear mixing action.
4. Micro mixing.

Answer: 2. Macro mixing

Question 8. Which of the following does not come under mixing in dispensing?

1. Trituration
2. Tumbling
3. Spatulation
4. Sizing

Answer: 4. Sizing

Question 9. Which one of the following equipment produces tumbling as a mechanism in a solid mechanism?

1. Fluidized mixer
2. Sigma blender
3. Ribbon blender
4. V-cone blender

Answer: 3. Ribbon blender

Question 10. Silverson mixer is used for the preparation of

1. Emulsion
2. Syrup
3. Suspension
4. Elixir

Answer: 1. Emulsion

Drying in Pharmaceutical Engineering Introduction

Drying is defined as the removal of small amounts of water or other liquid from a material by the application of heat.

• Adjustment and control of moisture levels in solid materials through drying is a critical process in the manufacture of many types of pharmaceutical products.
• As a unit operation, drying solid materials is one of the most common and important in the pharmaceutical industries, since it is used practically in every plant and facility that manufactures or handles solid materials, in the form of powders and granules.
• The effectiveness of drying processes can have a large impact on product quality and process efficiency.
• Drying normally occurs as a batch process, drying is a key manufacturing step.
• The drying process can impact subsequent manufacturing steps, including tab letting or encapsulation, and can influence critical quality attributes of the final dosage form.
• Apart from the obvious requirement of drying solids for a subsequent operation, drying may also be carried out to improve handling characteristics, as in bulk powder filling and other operations involving powder flow; and to stabilize moisture-sensitive materials.
• Drying differs from evaporation in that evaporation involves the removal of large amounts of liquids whereas in the case of drying the removal of a small amount of water occurs.

Moisture may be present in two forms in the product:

• Bound moisture: This is water retained so that it exerts a vapor pressure less than that of free water at the same temperature. Such water may be retained in small capillaries, adsorbed on surfaces, or as a solution in cell walls.
• Free moisture: This is water which is more than the equilibrium moisture Content‘„

Drying in Pharmaceutical Engineering Objectives

To transform the product into an acceptable form that will be useful for further processing

• To reduce the transportation cost drying reduces the weight of the product.
• To improve the physical and chemical stability of the product. Generally, the presence of moisture increases the rate of reactions. Also, it increases the chances of microbial attack.
• To improve some characteristics like the flow of powder from the hopper, compressibility, and size reduction.

Drying Applications in Pharmaceutical Engineering

In the pharmaceutical industry, it is used as a unit process in the manufacture of granules which can be dispensed in bulk or converted into tablets or capsules.

• In the process of tablet coating drying is also involved. It becomes very important to maintain the speed of drying.
• Drying can also be used to reduce the bulk and weight of the material, thereby lowering the cost of transportation and storage.
• It helps in the preservation of crude drugs of plants from mold growth, which occurs due to the presence of moisture.
• It helps in the size reduction of crude drugs. The presence of moisture in the crude drug does not allow it to get powdered easily.
• Preservation of products like blood products, and drugs of animal or plant origin.
• Drying is also used in the processing of materials for example The preparation of dried aluminum hydroxide, the spray drying of lactose, and the preparation of solid extracts.

Drying Process Mechanism in Pharmaceutical Engineering

The mechanism of the drying process involves both heat transfer and mass transfer processes simultaneously.

• Heat transfer takes place from the heating medium to the solid material.
• Mass transfer involves the transfer of moisture to the surface of the solids and subsequently vapourization from the surface into the surroundings.

Various theories are proposed to explain the movement of moisture. These are given below

1. Diffusion theory
2. Capillarity theory
3. Pressure gradient theory

Gravity flow theory and Vaporization and condensation mechanism

1. Diffusion Theory

Diffusion theory assumes that the effect of capillarity, gravitational, and friction forces are too small. According to this theory, the rate of drying is directly proportional to the amount of moisture present in the product.

The moisture movement takes place as follows:

• Water diffuses through the solid to the surface and subsequently into the surrounding
• Evaporation of water occurs at an intermediate zone, much below the solid surface then vapors diffuse through the solid into the air

Due to limitations in predicting the drying rate theory is not much applicable. over a range of moisture gradients, this

Diffusion Limitations:

Diffusivity decreases as the moisture content and temperature decrease while increasing with pressure.

2. Capillarity Theory

Capillarity theory applies to porous granular materials. The porous material contains a network of interconnected pores and channels. As the drying starts, a meniscus is formed in the capillary and exerts a force.

• This is the driving force for the movement of water through pores towards the surface. The curvature of the meniscus depends on the pore diameter and determines the strength of capillary force.
• The capillary action is greater in small pores than the large pores.
• Therefore, small pores pull more v/ater from the larger pores and thus large pores get emptied first Air enters into the emptied pores and the moisture content is relatively higher near the surface.
• The capillary theory holds good only for free water in the bed. This type of movement of liquid takes place in the granules (pores) as well as in the spaces between the granules (void spaces).

As the pore diameter is considerably smaller inside a granule than the surrounding granules, the liquid surrounding the granules can be removed initially. Then pore liquid inside a granule is vapourized. Diffusion theory applies to hygroscopic material.

3. Pressure Gradient Theory

Pressure gradient theory applies to the drying of solids by the application of radiation (not external heating).

• Radiation is a source for generating internal heat. The radiation interacts with the polarized molecules and ions of the material.
• This field aligns the molecules in order, which are otherwise randomly oriented. When the field is reversed, the molecules return to their original orientation.
• In this process, it gives up random kinetic energy (or heat) to the inside surface of the solids itself. Therefore, the liquid inside the solids is vapourised.
• As a result, the vapor pressure gradient is developed which is the driving force for the movement of the surface.
• This type of drying mechanism applies to radiation drying and mass vapor to ensure such rays penetrate deep inside the solid

Drying Methods in Pharmaceutical Engineering

The following are some general methods of drying:

Application of Hot Air (Convective or Direct Drying):

Air heating increases the drying force for heat transfer and accelerates drying. It also airs relative humidity, further increasing the driving force for drying.

• In the falling rate period, as moisture content falls, the solids heat up and the higher temperatures speed up the diffusion of water from the interior of the solid to the surface.
• However, product quality considerations limit the applicable rise in air temperature.
• Excessively hot air can almost completely dehydrate the solid surface so that its pores shrink and are almost close, leading to crust formation or “case hardening”, which is usually undesirable.

Indirect or Contact Drying (Heating through a Hot Wall):

As drum drying, and vacuum drying. Higher wall temperatures will speed up drying but this is limited by product degradation or case-hardening.

Dielectric drying:

Dielectric drying (radiofrequency or microwaves being absorbed inside the material) is the focus of intense research nowadays. It may be used to assist in air drying or vacuum drying. Researchers have found that microwave finish drying speeds up the otherwise very low drying rate at the end of the classical drying methods.

Freeze Drying or Lyophilization:

Freeze drying is a drying method where the solvent is frozen before drying and is then sublimed, i.e., passed to the gas phase directly from the solid phase, below the melting point of the solvent.

• It is increasingly applied to dry foods, beyond its already classical pharmaceutical or medical applications.
• It keeps the biological properties of proteins and retains vitamins and bioactive compounds. Pressure can be reduced by a high vacuum pump (though freeze-drying at atmospheric pressure is possible in dry air).
• If using a vacuum pump, the vapor produced by sublimation is removed from the system by converting it into ice in a condenser, operating at a very low temperature, outside the freeze-drying chamber.

Supercritical Drying (Superheated Steam Drying):

It involves steam drying of products containing water.

• This process is feasible because water in the product is boiled off, and joined with the drying medium, increasing its flow.
• It is usually employed in closed circuits and allows a proportion of latent heat to be recovered by recompression, a feature that is not possible with conventional air drying, for instance.
• The process has the potential for use in foods if carried out at reduced pressure, to lower the boiling point.

Natural Air Drying:

It takes place when materials are dried with unheated forced air, taking advantage of its natural drying potential.

• The process is slow and weather-dependent, so a wise strategy “fan OFF-fan ON” must be devised considering the following conditions:
• Air temperature, relative humidity and moisture content, and temperature of the material being dried.
• Grains are increasingly dried with this technique, and the total time (including fan off and on periods) may last from one week to various months.

Equilibrium Moisture Content (EMC) in Pharmaceutical Engineering

When a wet solid is brought into contact with a stream of air such that the temperature and humidity of the air are maintained constant and if the period of exposure is sufficiently long until equilibrium is reached, the material attains a definite moisture content that will be unchanged by further exposure to this same air.

This is known as the equilibrium moisture content (EMC) of the material under the specified conditions.  If the material contains more moisture than EMC, it will dry (desorption) until EMC is reached.

On the other hand, if it contains less moisture than EMC, it will absorb water (adsorption) until EMC is reached.

In some cases, EMC on the desorption and sorption curves are somewhat different:

• For the air of zero humidity, the EMC of all materials is zero.
• For any given percentage humidity of the carrier gas, EMC varies greatly with the type of material.
• A non-porous and non-hygroscopic, insoluble solid like sand will have an EMC of zero for any humidity and temperature.
• On the other hand, fibrous structures will have widely varying EMC under the same conditions of temperature and humidity.
• EMC of solids decreases with an increase in air temperature. From the above considerations, it can be understood that any material can be dried only up to EMC under a given set of conditions and not below it more
• Free moisture content (FMC) is the moisture present in the sample above EMC and it is the FMC that is removed in any drying operation. It may include bound and unbound water also.
• A simple static procedure to determine EMC is to place the samples in ‘laboratory desiccators containing sulphuric acid solutions of known concentration which produce an atmosphere of known relative humidity.
• The sample in each desiccator is weighed periodically until a constant weight is obtained.
• The final moisture content is the EMC. The desiccators may be placed at the required temperature.
• A dynamic method of determining EMC is to place a sample in a U-tube and draw a continuous flow of controlled humidity air until constant weight is reached.

Determination of Equilibrium Moisture Content:

Solid samples are placed in a series of closed chambers such as desiccators. Each chamber consists of a desiccant solution that maintains a fixed relative humidity in the enclosed air space i.e., the solids are exposed to several humidity conditions. The exposure is continued till the solid attains a constant weight.

The difference in initial and final weight is the moisture content:

1. Humidity: Mass of water carried per unit mass of dry air.
2. Saturation Humidity: This is the mass of water carried/unit mass of dry air where the air is completely saturated with water.

The moisture content of the solid can be expressed on wet weight basis or dry-weight basis. On a wet wet-weight basis, the water content is expressed as a percentage of the weight of the wet solid whereas on a dry dry-weight basis it is expressed as a percentage of the weight of the dry solid. LOD is an expression of moisture content on wet wet-weight basis.

EMC Application :

The EMC curve permits the selection of the experimental conditions to be used for drying the product.

• Drying should be stopped when the moisture content reaches the level of the EMC under the exposed conditions.
• Overdrying should be avoided because over-dried solids quickly regains moisture from the ambient conditions.
• If the moisture content is. to be reduced, the relative humidity of the ambient air must be reduced as a first step.
• This can be done mechanically on a large scale using an air conditioning system. On a small scale, desiccators are employed.
• Some materials, such as tablet granules, have superior compaction properties with a small amount (1-2%) of residual moisture content

Drying Equipment in Pharmaceutical Engineering

There are. number of instruments available for drying purposes.

They are classified as follows:

1. based on the mechanism of drying:

1. Static bed dryer: 
   • Example: Tray dryer, freeze dryer
2. Moving bed dryer:
   • Example: Drum dryer 1
3. Fluidized bed dryer: 
   • Example: Fluidized bed dryer
4. Pneumatic dryer:
   • Example: Spray dryer.

2. Based on contact with material:

1. Direct dryers (direct contact between wet solid and hot gases)
   1. Batch dryers:
      • For example: Tray dryers.
   2. Continuous dryers:
      • For example: Spray dryer, fluidized bed dryer.
2. Indirect dryers
   1. Batch dryers:
      • For example:  Freeze drying, vacuum tray dryer.
   2. Continuous dryers:
      • For example: Drum dryers.

Tray Dryer in Pharmaceutical Engineering

The simplest form of the dryer in this category is a laboratory oven.

• These ovens are not very beneficial because there is no controlling system over heat transfer or humidity.
• If a fan is fitted to the oven the forced hot air is circulated which helps in increasing the heat transfer and also in reducing the local vlour concentrations.
• Despite this, there is no adequate control.
• The best type of tray dryer is that of the directed circulation form, in which the air is heated and is directed across the material in a controlled flow.
• The material to be dried is spread on the tiers of the trays.
• The trays used have solid perforated or wire mesh bottoms.
• In a modern tray dryer, a uniform temperature and air is- maintained by the use of a well insulated cabinet with strategically placed fans and heating coils.
• There is an alternate arrangement of the shelves so that air can flow uniformly without any obstructions.
• Heater is fixed in such a way that the air is reheated before passing over each shelf.
• When the air passes over each shelf a certain amount of heat is given up to provide latent heat of vapourisation.
• In such type of dryers there can be a good control of heat and humidity provided it is designed correctly.

Tray dryer Principle:

Hot air is circulated over the material. Moisture is removed from the material by forced convection. Simultaneously some moist air of the dryer is continuously replaced with fresh air.

Tray dryer Construction:

It consists of a double-walled rectangular chamber. In between walls, the insulator material is present. The trays are arranged inside the heating chamber.  The number of trays may vary with the size of the dryer. Dryers of laboratory size may contain a minimum of three trays, whereas dryers of industry size may contain more than 20 trays.

The distance between the bottom of the upper tray and the surface of the substance loaded in the subsequent tray must be 40 mm. Electric heaters are provided for heating. Fans are fitted in the heating chamber to circulate the hot air over all the trays. In the corner of the chamber direction vanes are placed to direct air in the expected path.

Tray dryer Working:

Trays loaded with wet material are placed in the chamber. Fresh air is introduced through inlet, which gets heated by heaters. The hot air is circulated using fans. The speed of fans is generally kept between 2 to 5 meters per second.

Turbulent flow lowers the partial vapor pressure in the atmosphere. The drying of the material occurs at its surface due to hot air circulation. As the surface water evaporated the remaining moisture of the material which was inside comes on due to capillary action.

These events occur in a single pass of air. The hot air cannot pick up enough air at a single pass as the time of contact is less. So it is recirculated along with 20% of the fresh air. Moist air is discharged through the outlet. Thus constant temperature and uniform air flow over the materials can be maintained for achieving uniform drying.

Tray dryer Uses:

• A tray dryer is used for the drying of sticky materials.
• Tray dryers are used in the drying of the granular mass or crystalline materials.
• Plastic substances can be dried by the tray dryers.
• Wet mass preparations, precipitates, and pastes can be dried in a tray dryer.
• In the tray dryers the crude drugs, chemicals, powders, and tablet granules are also dried and show the free flow of the materials by picking up the water.
• Some types of equipment can also be dried in the tray dryers.

Tray dryer Advantages:

• The tray, dryer is operated batch-wise. Batch drying allows the handling of material as a separate part.
• So mistakes in the previous batch cannot continue in the next batch.
• A wide variety of materials can be dried.

Tray dryer Disadvantages:

• A tray dryer requires more labor to load and unload. Hence increase in the cost.
• The process is time-consuming.

Drum Dryer in Pharmaceutical Engineering

The drum dryer is the equipment used to convert the solutions and suspensions into the solids. The main purpose of this dryer is to spread the liquid to a large surface area so that drying can occur rapidly. It is also called an roller dryer or film drum dryer. The drum dryer consists of a hollow roller with a smoothly polished external surface heated internally by steam. It rotates on its longitudinal axis. The liquid to be dried is placed in a trough known as a feed pan. The liquid is picked up by the roller as it rotates covering the surface and a thin film is removed mechanically by a scrapper known as a doctor knife

Drum dryer Principle:

In the drum dryer, the drum rotates on its longitudinal axis which is a heated hollow metal drum, this metal drum is dipped in the solution to be dried. As the dipping process is completed the solution on the drum forms a film on the surface of the dryer and is made to dry, to form a layer on the surface of the metal drum. While the drum is rotating the suitable knife which is present just down the metal drum scraps or peels off the dried materials from the drum.

Drum dryer Construction:

It consists of a hollow steel drum of 0.6 to 3 metres diameter and 0.6 to 4.0 m length which is horizontally mounted and its external surface is smoothly polished for the easy removal of the dried cake.

Below the drum, a pan is placed with the feed in the manner that the drum dips partially into the pan consisting of feed. On one side of the drum a spreader is placed which is used to spread the material onto the drum and on the other side a knife is placed to scrape or peel off the dried material from the metal drum. After peeling the material collect the material, in the conveyor or storage bin.

Drum dryer Working:

The drying of the material is done by the process of steam when passed into the drum. Due to the metallurgic nature of the drum, the heat absorption is higher.

• By the mechanism of conduction, the heat gets transferred into the drum and the drying process takes place, the drying capacity is directly proportional to the drum surface area.
• The liquid material that is present in the pan gets adhered to the drum and gets dried by revolving at the rate of 1 to 10 revolutions.
• The material is completely dried during its journey during its revolutions. The dried material is scrapped by the knife and falls into the bin.

Drum dryer Uses:

• Solutions, slurries, suspensions, and more are dried in this dryer.
• Milk products, starch products, ferrous salts, suspensions of zinc oxide, suspensions of kaolin, yeast, pigments, malt extracts, antibiotics, glandular extracts, insecticides, DDT, calcium, and barium carbonates are dried in this dryer

Drum dryer Advantages:

• It takes less time to dry.
• Heat-sensitive drugs can also be dried.
• It requires less area.
• To reduce the temperature of drying, the drum can be enclosed in a vacuum chamber.
• Rapid drying takes place due to rapid heat and mass transfer.

Drum dryer Disadvantages:

• Maintenance costs are high.
• Skilled operators are essential to maintain thickness control of the film.
• It is not suitable for products having less solubility

Spray Dryer in Pharmaceutical Engineering

A spray dryer is a device that is used for drying all types of materials mostly thermolabile, hygroscopic drugs, or materials that undergo chemical decomposition.

A typical spray dryer consists of a drying chamber which is just like the cyclone separator, to ensure good circulation of air to facilitate heat and mass transfer and also to ensure that the dried particles are separated by the centrifugal action.

Two types of atomizers are used, they are:

1. Jet atomizer
2. Rotary atomizer

Jet atomizer is easily blocked resulting in variation of the droplet size. Rotary atomizer are preferred to avoid this problem.

Spray dryer Principle:

In the spray dryer, the fluid to be dried is converted to fine droplets, which are thrown radially into a moving stream of hot gas. The temperature of the droplets is increased and . droplets get dried in the form of spherical particles. The droplets get dried completely before they reach the wall of the dryer.

Spray dryer Construction:

The construction of the spray dryer consists of a large cylindrical drying chamber made up of stainless steel. It has a narrow bottom. The diameter of the drying chamber ranges between 2.5 to 9 m and the height is about 25 m or more.

At the roof, two inlets are fixed one is for hot air and another is for fluid which is to be dried. The second inlet is fitted with a spray disk atomizer. The spray disk atomizer is about 300 mm in diameter and rotates at a speed of 3000 to 50000 revolutions per minute. The bottom of the dryer is connected to a cyclone separator.

Spray dryer Working:

Drying of the materials in the spray dryer involves three stages

1. Atomization of the liquid.
2. Drying of the liquid droplets.
3. Recovery of the dried products

Atomization of the liquid to form liquid droplets: The feed is introduced through the atomizer either by gravity or by using a suitable pump to form fine droplets. The selection of atomizers is important as it affects the quality of the final product. The rate of feed is adjusted in such a way that the droplets should be completely dried before reaching the walls of the drying chamber. Atomizers of any type like pneumatic atomizers, pressure nozzle, and spinning disc atomizers may be used.

Spray dryer of the liquid droplets:

Through the inlet hot air is supplied which causes the drying of fine droplets. The surface of the liquid drop is dried immediately forming a tough shell. The liquid inside gets dried by the diffusion. water inside the droplet comes towards the surface and gets evaporated.

• At the same time heat transfer from outside to inside takes place at a rate greater than the liquid diffusion rate. As a result, heat enters inside the liquid to evaporate at a faster rate.
• This tendency of a liquid leads to a rise in the internal pressure which causes the droplets
  to swell.
• The shell thickness decreases where as permeability for vapour increases. If the shell is neither elastic nor permeable it ruptures and the internal pressure escapes.
• The temperature of the air is adjusted in such a way that the droplets should be completely dried before reaching the walls of the drying chamber.
• The products should not be overheated at the same time.

Spray dryer Recovery of the dried products:

The droplets of the liquid follow a helical path due to the centrifugal force of the atomizer. Particles are dried during their journey and finally fall at the conical bottom. All these processes are completed in a few seconds. The particle size of the final products ranges from the 2 to 500 micrometers. Particle size is dependent on solid content in the feed, liquid viscosity, feed rate, and disc speed.

Spray dryer Uses:

• It can be used for drying many substances both in solution and in suspension.
• It is very useful for the drying of heat-sensitive materials.
• Citric acid, borax, sodium phosphate, hexamine, gelatine, and extracts are dried by a spray dryer.
• The suspensions of starch, barium sulfate, and calcium phosphate are also dried by the spray dryer.
• Milk, soap, and detergents too are dried by a spray dryer.
• The product is in a better form than that obtained by any other dryer.
• The quantity of the materials to be dried is large.
• The product is hygroscopic or undergoes chemical decomposition.

Spray dryer Advantages:

• It is a very rapid process.
• It is cost-effective as it performs the function of an evaporator, crystallizer, dryer, size reduction unit, and classifier
• By using a suitable atomizer the products of uniform and controlled size can be obtained. Free-flowing products of uniform spheres is formed which is very convenient for tablet processing.
• A fine droplet formed provides a larger surface area for heat and mass transfer.
• The product shows excellent solubility.
• Either the solutions or suspensions are thin paste. and can be dried in one step to get the final product ready for the package.
• It is suitable for the drying of the sterile products.
• Globules of an emulsion can be dried with the dispersed phase inside and a layer of the continuous phase outside. On the reconstitution, the emulsion will be formed.

Spray dryer Disadvantages:

• The spray dryer is very bulky and expensive.
• The thermal efficiency is low, as much heat is lost in the discharged gases.

Fluidized Bed Dryer in Pharmaceutical Engineering

In a fluid bed dryer, good contact between hot air and particles to be dried so obtained which causes rapid drying.

 Fluid Bed Dryer Theory:

If a gas is allowed to flow upwards through a bed of solids particles at a velocity greater than the setting velocity of the particles, the particles are partially suspended in the gas stream. The resultant mixture of solids and gas behaves like a liquid and the solids are said to be fluidized.

Each solid particle is surrounded by the drying gas v/ith the result that the drying taking place in a much shorter period. Moreover, the intense mixing between the solid and hot air provides a uniform condition of temperature, composition, and particle, size distribution.

Two types of fluidized bed dryers are used in the pharmaceutical industry. These are:

1. Vertical fluidized bed dryers
2. Horizontal fluidized bed dryers

 Fluid bed dryer Principle:

In the fluidized bed dryer, hot air or gas is passed at high pressure through a perforated bottom of the container containing granules to be dried. The granules get suspended due to the high speed of air that enters from the bottom of the container. This condition is called a fluidized state.

As the particles are completely suspended they do not have any kind of physical contact with any particle or surface of the container. So they get surrounded with hot air. Thus material or granules are uniformly dried from all the surfaces.

 Fluid bed dryer Construction:

There are two types of fluidized bed dryers.

1. Vertical fluidized bed dryers.
2. Horizontal fluidized bed dryers.

The construction of the vertical fluidized bed dryer is made up of stainless steel or plastic. A detachable container is placed at the bottom of the dryer, which has to be filled with the material which has to be dried. This container has a perforated bottom with a wire mesh support for placing the materials to be dried. A fan is mounted in the upper part for circulating hot air.

Fresh air inlet, prefilter, and heat exchanger. are connected serially to heat the air to the required temperatures.

• Above the container bag filters are attached to collect the fines or granules.
• After a specific period or after drying of granules the drying chamber is removed from the unit for the removal of dried material.
• It is again filled for the fresh material to be dried (batch process).
• The different capacities ranging from 5 kg to 200 kg with an average drying time of about 20-40 min. of fluidized bed dryers are available.
• Horizontal vibrating conveyor fluidized bed dryers are used for continuous drying of large volumes of the material.

 Fluid bed dryer Working:

The wet material to be dried is placed in a container. The container is pushed into the dryer. Fresh air is allowed to pass through a prefilter, which subsequently gets heated by passing through a heat exchanger.

• The hot air is supplied through the bottom of the container. Simultaneously fan is allowed to rotate.
• The air velocity is gradually increased to suspend the particles of material.
• After some time the granules rise in the container because of high-velocity gas and again fall. This condition is called a fluidized state.
• The gas surrounds every granule to completely dry them. The air leaves the dryer through the bag filter.
• The particles of air get entrapped in the bag filters. After a regular interval, the bags are shaken to remove the entrapped particles.
• Intense mixing between the granules and hot gas is provides uniform conditions of the temperature, composition, and particle size distribution.
• Drying is achieved at a constant rate and the falling period is very short. The average drying time for the material is about 40 min. The material is left for sometime in the dryer for cooling.

Fluid bed dryer Uses:

• It is used in tablet processing for drying the granules.
• It is a multipurpose instrument and can be used for the three operations such as.
• mixing, granulation, and drying

Fluid bed dryer Advantages:

• It is fast takes less time than a tray dryer.
• Handling time is also short. It is 15 times faster than the tray dryer.
• It is available in different sizes with a drying capacity ranging from 5 to 200 kg per
  hour.
• The drying containers are mobile, making handling simple and reducing labor costs.
• The thermal efficiency is 2 to 6 times greater than the tray dryer.
• It is also used for mixing the ingredients and its mixing efficiency is also high.
• Hot spots are not observed in the dryer because of its excellent mixing and drying
  capacities.
• As contact time is short it can be used for drying heat-sensitive materials.
• It can be used either as batch type or continuous type.

Fluid bed dryer Disadvantages:

• Many organic powders develop electrostatic charges during drying.
• To avoid this efficient electrical earthing of the dryer is essential.
• The turbulence of the fluidized state of granules may cause attrition of some materials resulting in the production of fines.

Vacuum Dryer in Pharmaceutical Engineering

The vacuum dryer which is in common use in the pharmaceutical industry is called a vacuum oven. It consists of a jacketed vessel made of materials that can withstand vacuum within the oven and steam pressure in the jacket.

The oven is generally operated at a pressure of about 0.03 to 0.0At this pressure water boils at 25-35 degrees centigrade. In the pharmaceutical industry, an oven of the size of about 1.5 m cubes having 20 shelves is commonly used.

Nowadays vacuum ovens with several small compartments with small doors are available rather than one big compartment with a heavy door.

 Vacuum dryer Principle:

In a vacuum dryer material is dried by using a vacuum. Due to the application of vacuum, the liquid boils at a lower temperature than the boiling point. So evaporation of liquid takes place faster and at low temperatures.

 Vacuum dryer Construction:

The construction of vacuum dryer is made up of an iron-heavy jacketed vessel that can withstand the steam pressure in the jacket. The inside space is divided into 20 hollow shelf portions which are part of the jacket.

These shelves provide increased conduction of heat due to the larger surface area and metal trays are placed over the shelves to keep the material. The oven door is locked tightly to give an air-tight seal and is connected to a vacuum pump by placing a condenser

Fluid bed dryer Working:

The trays which are present in the dryer are used to dry the material that is placed on the shelves and the pressure is decreased up to 30 to 60 kps by a vacuum pump. The door is closed firmly and steam is passed through the space of the jacket and shelves.

So heat transfer takes place by the mechanism of conduction. Be vacuum evaporation the water is taken out from the material at 25 – 30 °C. Water vapour passes into the condenser and after drying vacuum line is disconnected then the materials are collected from the trays.

Fluid bed dryer Uses:

Vacuum dryer can be used for drying the following Heat heat-sensitive materials, dusty materials, hygroscopic materials, and toxic materials can be dried in this vacuum dyer.

Feed materials containing the solvents are also dried by this vacuum dryer. The solvent material can be recovered by the condensation process. Drugs that are required as porous end products. Friable dry extracts can be obtained through this drying process.

 Fluid bed dryer Advantages:

• Handling of the materials is easy in this drying because of the tray arrangement inside the dryer.
• It is easy to switch over to the next materials.
• Hollow shelves which are electrically heated can be used.
• It provides a large surface area. So the heat can be easily transferred throughout the body of the dryer and fast drying action takes place.
• Hot water can be supplied throughout the dryer which helps in the drying process at the
  desired temperature.

 Fluid bed dryer Disadvantages:

• The dryer is a batch-type process.
• It has low efficiency.
• It is more expensive.
• Labor cost is too high for the running of the dryer.
• Maintaining the dryer is high.
• There is a danger of overheating due to the steam produced.
• Heat transfer is low in a vacuum dryer.

Freeze Drying in Pharmaceutical Engineering

Freeze drying Principle:

The main principle involved in freeze drying is a phenomenon called sublimation, where water passes directly from the solid state (ice) to the vapor state without passing through the liquid state. Sublimation of water can take place at pressure and temperature below triple point i.e. 4.579 mm of Hg and 0.0099°C.

The material to be dried is first frozen and then subjected under a high vacuum to heat (by conduction or radiation or by both) so that frozen liquid sublimes leaving only solid, dried components of the original liquid.

The concentration gradient of water vapor between the drying front and condenser is the driving force for the removal of water during lyophilization. The principle of freeze/sublimation-drying is based on this physical fact. The ice in the product is directly converted into water vapor (without passing through the “fluid state”) if the ambient partial water vapor pressure is lower than the partial pressure of the ice at its relevant temperature.

Freeze drying Equipment:

The equipment for freeze-drying consists of following parts

• Drying chamber in which trays are located.
• Heat supply in the form of radiation source, heating coils.
• Vapor condensing or adsorption system.
• Vacuum pump or steam ejector or both.

The chamber for vacuum drying is generally designed for batch operation. It consists of shelves for keeping the material. The distance between the subliming surface and condenser must be less than the mean path of molecules. This increases the rate of drying.

The condenser consists of a relatively large surface cooled by solid carbon dioxide slurred with acetone or ethanol. The temperature of the condenser must be much lower than the evaporated surface of the frozen substance. To maintain this condition, the condenser surface is cleaned repeatedly.

Freeze-drying process:

Freeze drying is mainly used to remove the water from sensitive, products, mostly of biological origin, without damaging them, so they can be preserved easily, in a permanently storable state, and be reconstituted simply by adding water.

Examples of freeze-dried products are – Antibiotics, Bacteria, Sera, Vaccines, Diagnostic medications, etc.

Freeze drying process involves the following steps:

1. Pretreatment
2. Prefreezing
3. Primary drying
4. Secondary drying
5. Packing

1. Pretreatment:

• Pretreatment includes any method of treating the product before freezing.
• This may include concentrating the product, formulation revision (i.e., the addition of components to increase stability and/or improve processing), decreasing a high vapor pressure solvent or increasing the surface area.
• In many instances the decision to pretreat a product is based on theoretical knowledge of freeze-drying and its requirements or is demanded by cycle time or product quality considerations.

2. Prefreezing:

Since freeze drying is a change in state from the solid phase to the gaseous phase, the material to be freeze-dried must first be adequately frozen.

• The method of freezing and the final temperature of the frozen product can affect the ability to successfully freeze dry the material.
• Rapid cooling results in small ice crystals, useful in preserving structures to be examined microscopically, but resulting in a product that is more difficult to freeze dry.
• Slower cooling results in larger ice crystals and less restrictive channels in the matrix during the drying process.
• Most samples are a mixture of substances that freeze at a lower temperature than the surrounding water.
• When the aqueous suspension is cooled, changes occur in the solute concentrations of the product matrix.

As cooling proceeds, the water is separated from the solutes as it changes to ice,
creating more concentrated areas of solute. These pockets of concentrated material have a lower freezing temperature than the water.

• Although a product may appear to be frozen because of all the ice present, in reality, it is not completely frozen until all of the solute in the suspension is frozen.
• The mixture of various concentrations of solutes with the solvent constitutes the eutectic of the suspension.
• Only when all of the eutectic mixtures are frozen the suspension is properly frozen. This is called the eutectic temperature.
• It is very important in freeze drying to pre-freeze the product to below the eutectic temperature before beginning the freeze drying process.
• Small pockets of unfrozen material remaining in the product expand and compromise the structural stability of the freeze-dried product.
• The second type of frozen product is a suspension that undergoes glass formation during the freezing process.
• Instead of forming eutectics, the entire suspension becomes increasingly viscous as the temperature is lowered.

Finally, the product freezes at the glass transition point forming a vitreous solid. This type of product is extremely difficult to freeze to be freeze-dried are eutectics, which are dry.

3. Primary drying:

In this step ice formed during the freezing is removed by sublimation under vacuum at low temperature, leaving a highly porous structure in the remaining amorphous solute that is typically 30% water.

• This step is carried out at a pressure of 10“4 to 10″5 atmospheres, and a product temperature of 45 to 20°C.
• Sublimation during primary drying is the result of coupled heat- and mass-transfer processes.
• After the freezing step has been completed, the pressure within the freeze-dryer is reduced using a vacuum pump.
• Typical chamber pressure in the lyophilization of pharmaceuticals ranges from 30 and 300 motors and depends on the desired product temperature and the characteristics of the container system.
• The chamber pressure needs to be lower than the vapor pressure of ice at the sublimation interface in the product to facilitate the sublimation of ice and transport of water vapor to the condenser where it is deposited as ice.

Very high chamber pressure decreases the sublimation rate by reducing the pressure gradient between the sublimation interface and chamber, thereby mitigating the driving force for sublimation and continuing removal of ice.

• If the chamber pressure exceeds the vapor pressure at the sublimation interface, no mass transfer is possible.
• On the other hand very low pressure  50 meters) are also counterproductive for fast sublimation rate since they greatly limit the rate of heat transfer to the product.
• Once the chamber pressure decreases below the vapor pressure of ice in the product, sublimation can occur, i.e. ice is removed from the top of the frozen layer and directly converted to water vapor.
• Water vapor is transported to the ice condenser and deposited onto the coils or plates which are constantly cooled to a temperature associated with very low vapor pressure of the condensed ice.
• The sublimation of water from the product requires energy (temperature-dependent, around – 670 cal/g), leading to cooling of the product.
• The energy for continuing sublimation of ice needs to be supplied from the shelves that are heated to a defined higher temperature.
• The product temperature is in general the most important product parameter during a freeze drying process, in particular the product temperature at the sublimation interface during primary drying.

4. Secondary drying

After primary freeze-drying is complete, and all ice has sublimed, bound moisture is still
present in the product.

• The product appears dry, but the residual moisture content may be as high as 7 – 8% continued drying is necessary at warmer temperatures to reduce the residual moisture content to optimum values.
• This process is called “Isothermal Desorption” as the bound water is desorbed from the product.
• Secondary drying is normally continued at a product temperature higher than ambient but compatible with the sensitivity of the product.
• In contrast to processing conditions for primary drying which use low shelf temperature and a moderate vacuum, desorption drying is facilitated by raising shelf temperature and reducing chamber pressure to a minimum.
• Care should be exercised in raising shelf temperature too highly; since protein polymerization or biodegradation may result from using high processing temperature during secondary drying.
• Secondary drying is usually carried out for approximately 1/3 or 1/2 the time required for primary drying.
• The general practice in freeze-drying is to increase the shelf temperature during secondary drying and to decrease chamber pressure to the lowest attainable level.

5. Packing:

After the vacuum is replaced by inert gas, the bottles and vials are closed.

Freeze-drying Uses:

• It is used for drying of number products such as:
• Blood plasma and blood products.
• Bacterial and viral cultures.
• Human tissue.
• Antibiotics and plant extracts

Freeze-drying Advantages:

• Oxidizable substances are well protected under vacuum conditions.
• Long preservation period owing to 95% – 99.5% water removal.
• Loading quantity is accurate and content uniform.
• Little contamination owing to the aseptic process.
• Minimal loss in volatile chemicals heat-sensitive nutrients and fragrant
  components.
• Minimal changes in the properties because microbe growth and enzyme effect cannot be exerted under low temperatures.
• Transportation and storage under normal temperature.
• Rapid reconstitution time.
• Constituents of the dried material remain homogenously dispersed.
•  The product is processed in the liquid form.
• Sterility of the product can be achieved and maintained.-)

Freeze-drying Disadvantages:

• Volatile compounds may be removed by high vacuum.
• Single most expensive unit operation.
• Stability problems associated with individual drugs.
• Some issues associated with sterilization and sterility assurance of the dryer chamber and aseptic loading of vials into the chamber.

Drying in Pharmaceutical Engineering Multiple Choice Questions

Question 1. A fluidized bed dryer has one of the following advantages.

1. Attrition is not observed
2. The entire material is continuously exposed to a heat source
3. A fluffy mass is formed
4. Humidity can be increased

Answer:  2. The entire material is continuously exposed to a heat source

Question 2.  In a fluidized bed dryer, a prefilter is included for filtering one of the following.

1. Air
2. Fines
3. Moisture
4. Particles

Answer:  1. Air

Question 3.  Which part of the spray dryer controls the particle size of particle?

1. Atomizer
2. Cyclone separator
3. Fluid bed
4. Drying chamber

Answer:  1. Atomizer

Question 4. Which method you will use to dry blood plasma?

1. Tray dryer
2. Spray dryer
3. Drum dryer
4. Freeze drying

Answer:  4. Freeze drying

Question 5.  Which one of the following is an example of a pneumatic dryer?

1. Drum dryer
2. Fluidized bed dryer
3. Spray dryer
4. Freeze dryer

Answer:  3. Spray dryer

Question 6. Which of the following drying methods involves the principle of sublimation?

1. Freeze drying
2. Vacuum dryer
3. Fluidized bed drying
4. Spray drying

Answer: 1. Freeze drying

Question 7.  Which one of the following is called a lyophilizer?

1. Freeze dryer
2. Vacuum drying
3. Fluid bed dryer
4. Drum dryer

Answer: 1. Freeze dryer

Question  8. Eutectic point is an important factor for one of the following methods?

1. Drum dryer
2. Fluid bed dryer
3. Spray dryer
4. Freeze dryer

Answer:  4. Freeze dryer

Question 9. Drying is different from evaporation in which one of the following aspects?

1. The amount of liquid removed is less
2. High process temperature
3. Quantity of product is high
4. Less time required

Answer:  1. The amount of liquid removed is less

Question 10. In the drying process, when equilibrium moisture reaches the rate of drying becomes

1. High
2. Low
3. One
4. Zero

Answer: 4. Zero

Flow Of Fluids in Pharmaceutical Engineering Introduction

A substance that takes the shape of its container and flows from one location to another is called a fluid. The class of all materials that are fluids includes both liquids, such as water, and gases, such as air. The class of incompressible fluids is called liquids.

• Fluid flow is a part of fluid mechanics that deals with dynamics. Fluids such as gases and liquids in motion is called fluid flow.
• Fluid flow is an important aspect in various pharmaceutical industry processes, including large production-scale equipment applications, flows in laboratory devices used to analyze and develop drugs, and biological transport in the human body.
• To improve the development, production, analysis, and delivery of new therapies, efficient tools are needed to characterize, understand, and ultimately predict flow in relevant systems.
• Several factors motivate an improved understanding of these flows. Even more complex synthesis of drugs, tighter regulatory requirements, and the development of novel drug delivery systems involve increasingly sophisticated fluid flow.
• Fluid motion can affect several steps needed to produce a pharmaceutical product, thus highlighting the need to advance the study of fluid flows throughout the industry.
• Fluids can flow steadily, or be turbulent. In steady flow, the fluid passing through a given point maintains a steady velocity.
• For turbulent flow, the speed and or the direction of the flow varies. In steady flow, the motion can be represented with streamlines showing the direction the water flows in different areas. The density of the streamlines increases as the velocity increases fluids can be compressible or incompressible.

This is the big difference between liquids and gases, because liquids are generally incompressible, meaning that they don’t change volume much in response to a pressure change whereas gases are compressible, and will change volume in response to a change in pressure. Fluid can be viscous (pours slowly) or non-viscous (pours easily)

Laminar flow and turbulent flow:

Flow Of Fluids Manometers

A manometer is a device for measuring fluid pressure consisting of a bent tube containing one or more liquids of different densities. A known pressure (which may be atmospheric) is applied to one end of the. manometer tube and the unknown pressure (to be determined) is applied to the other end

Manometer operates on the hydrostatic balance principle. A basic manometer includes a reservoir filled with a liquid. The reservoir is usually enclosed with a connection point that can be attached to a source to measure its pressure. A transparent tube or column is attached to the reservoir.

• The top of the column may be open, exposing it to atmospheric pressure, or the column may be sealed and evacuated.
• Manometers that have open columns are usually used to measure gauge pressure or pressure about atmospheric pressure.
• Manometers with sealed columns are used to measure absolute pressure or pressure about absolute zero.
• Manometers with sealed columns are also used to measure vacuum.
• When a manometer is connected to a process, the liquid in the column will rise or fall according to the pressure of the source.
• It will, get measured. To determine the amount of pressure, it is necessary to know the type of liquid in the column, and the height of the liquid.
• The type of liquid in the column of a manometer will affect how much it rises or falls in response to pressure, its specific gravity must be known to accurately measure pressure.
• Manometers are accurate; they are often used as calibration standards.
• The shape of the liquid at the interface between the liquid and air in the column affects the accuracy of the manometer. This level is called the meniscus.
• The shape of the meniscus is determined by the type of liquid used.
• To minimize the errors that result from the shape of the meniscus, the reading must be taken at the surface of the liquid in the center of the column.
• The quality of the fill liquid will also affect the accuracy of pressure measurements. The fill liquid must be clean and have a known specific gravity.

Manometer Classification 

Broadly manometers are classified into two classes

1. Simple manometer:  Simple manometers are those that measure pressure at a point in a fluid contained in a pipe or a vessel.
   • Simple manometers are of many types:
     1. Piezometer
     2. U-tube manometer
     3. Single column manometer
2. Differential manometer:  Differential manometers measure the difference of pressure between any two points in a fluid contained in a pipe or vessel.
   • The differential manometer is of the following types:
     1. U-tube differential manometer
     2. Inverted U-tube differential manometer: This type of manometer is used for measuring the difference between two pressures (where accuracy is a major consideration).

1. Inclined manometer

1. Piezometer:

A piezometer is one of the simplest forms of manometer. It can be used for measuring the moderate pressure of liquids.

• • The setup of the piezometer consists of a glass tube, inserted in the wall of a vessel or of a pipe.
  • The tube extends vertically upward to such a height that liquid can freely rise in it without overflowing.
  • The pressure at any point in the liquid is indicated by the height of the liquid in the tube above that point.

Pressure at point A can be computed by measuring the height to which the liquid rises in the glass tube.

The pressure at point A is given by:

⇒ p = wh,

Where w is the specific weight of the liquid.

Limitations of Piezometer:

1. Piezometers can measure gauge pressures only. It is not suitable for measuring negative pressures
2. Piezometers cannot be employed when large pressure in lighter liquids is to be measured since this would require very long tubes, which cannot be handled conveniently.
3. Gas pressure cannot be measured with piezometers, because a gas forms no free
   atmospheric surface.

2. U-tube manometer:

The piezometer cannot be employed when large pressure in the lighter liquids is to be measured, since this would require very long tubes, which cannot be handled conveniently. Furthermore, gas pressure cannot be measured by the piezometers because a gas forms no free atmospheric surface.

These limitations can be overcome by the use of U-tube manometers.

1. A U-tube manometer consists of a glass tube bent in a U-shape, one end of which is connected to a point at which pressure is to be measured and the other end remains open to the atmosphere.
2. Using a “U’ Tube enables the pressure of both liquids and gases to be measured with the same instrument.
3. The “U” is filled with a fluid called the manometric fluid.
4. The fluid whose pressure is being measured should have a mass density less than that of the manometric fluid.

Characteristics of liquid used in U-tube Manometer:

• Viscosity should be low.
• Low surface tension is required.
• The liquid should stick to the walls.
• Should not get vaporized.
• The two fluids should not be able to mix readily that is, they must be immiscible.

U-tube Manometer Advantages:

• Simple in construction.
• Low cost hence easy to buy.
• Very accurate and sensitive.
• It can be used to measure other process variables.

U-tube Manometer Disadvantages:

• Fragile in construction
• Very sensitive to temperature changes

U-tube Manometer Applications:

• It is used for low-range pressure measurements.
• Extensively used in laboratories.
• Is used in orifice meters and venturi meters for flow measurements.
• It is used for the calibration of gauges and other instruments.
• It is used for measuring pressure drops in different joints and valves.

3. Single-column manometer (micromanometer):

The U-tube manometer described above usually requires the reading of fluid.

1. Levels at two or more points since a change in pressure causes a rise of the liquid in one limb of the manometer and a drop in the other.
2. This difficulty is however overcome by using single-column manometers.
3. A single-column manometer is a modified form of a U-tube manometer in which a shallow reservoir having a large cross-sectional area (about 100 times) as compared to the area of the tube is connected to one limb of the manometer,

 Single Column Manometer Advantages:

• Easy to fabricate and relatively inexpensive.
• Good accuracy.
• High sensitivity.
• Requires little maintenance.
• Not affected by vibrations.
• Specially suitable for low pressure and low differential pressures.
• It is easy to change the sensitivity by affecting a change in the quantity of manometric liquid in the manometer.

Limitations of Single Column Manometer:

• Usually bulky and large.
• Being fragile, gets broken easily.
• Readings of the manometer are affected by changes in temperature, altitude, and gravity.
• A capillary effect is created due to the surface tension of the manometric fluid.

2. Differential manometer

The differential manometer measures the difference of pressure between any two points in a pipe containing fluid. These are used to measure small pressure differences. It can also measure small gas pressures (heads). These manometers have extreme precision and sensitivity. These are free from errors due to capillarity and require no calibrations

Types of Differential Manometer:

The principle and working of the types of differential manometers are given below

U-tube Differential Manometer:

In the adjoining figure, the two points A and B are in liquids having different specific gravity. Also, A and B are at different levels. A liquid that is denser than the two fluids is used in the U tube, which is immiscible with the other fluids. Let the pressure at point A be PA and that at point B be PB.

P_A – P_B = 9 x h (ρ_g – ρ₁)

Where

h = Difference in mercury level in the U-tube

ρ_g = Density of heavy liquid

ρ₁ = Density of liquid A

Inverted U-tube Differential Manometer:

This type of manometer is used when the difference between the densities of the two liquids is small.

• Similar to the previous type, A and B are points at different levels with liquids having different specific gravity.
• It consists of a glass tube shaped like an inverted letter ‘U’ and is similar to two piezometers connected end to end.
• Air is present at the center of the two limbs. As the two points in consideration are at different pressures,
• The liquid rises in the two limbs.
• Air or mercury is used as the manometric fluid.

If PA is the pressure at point A and PB is the pressure at point B:

P_A-P_B = ρ₁ × g × h₁ -ρ₂ × g × h₁ × ρg  × g × h

ρ₁ = Density of liquid at A

ρ₂ = Density of liquid at B

ρ_g = Density of light liquid

h = Difference of light liquid

Where,

3. Inclined Type Manometer

It is similar to a well-type manometer in construction. The only difference is that the vertical column limb is inclined at an angle of 0. Inclined manometers are used for accurate measurement of small pressure.

Flow Of Fluids Bernoulli’s Theorem

When the principle of conservation of energy is applied to the flow of fluids, the resulting equation is called Bernoulli’s theorem.

• Bernoulli’s theorem is only a special case of the law of conservation of energy.
• Bernoulli’s theorem states that in a steady state ideal flow of an incompressible fluid.
• The total energy per unit mass, which consists of pressure energy, kinetic energy and datum energy, at any point of the liquid is constant.
• In simple terms, an increase in the velocity of fluid is compressed by a decrease of pressure.
• In most cases, the temperature in the fluid decreases as the fluid moves faster. Consider a system represented.

• It represents a pipe transferring a liquid from point A to point B. The pump supplies the energy to cause the flow. Consider that 1 lb liquid enters at point A. Let the
• Pressure at point A be PA lb force/sq.ft, let the average velocity of liquid be P_A fps and let the specific volume of liquid be V_A Cu ft/lb.
• Line MN represents the horizontal datum plain. Point A and B are at a height X_A and X_B respectively from the datum plane.
• The potential energy of a pound of liquid at A has potential energy equal to X_A ft-lb. The velocity of the liquid is XA ft-lb the kinetic energy of the liquid = U2_A ft-lb/ 2gc.
• A pound of liquid enters the pipe against a pressure PA lb force/ sq.ft.
• Therefore work done on a pound of liquid equal to P_A V_A ft lb is added to the energy. The total energy of the system is the sum of all the three energies.

Total energy = Potential energy + Kinetic energy + Pressure energy

The total energy of 1 lb of liquid at A ⇒ X_A  +U2_A/2gc + P_AV_A

After a steady state when one pound of liquid enters at point A another pound is displaced at B, according to the principle of conservation of mass.  It will have energy

⇒ X_B  +U2_B/2gc + P_BV_B

Where U_B, P_B, and VB are velocities, pressure, and specific volume respectively at point B.

If there are no additions or losses the energy content of one pound of liquid entering at A is exactly equal to its energy at B, according to principles of conservation of energy

⇒ X_A +U2_B/2gc + P_BV_B + P_AV_A

= X_B  +U2_B/2gc + P_BV_B

But some energy is added by the pump. Let this be equal to w ft. lb per lb of liquid. Some energy is lost due to friction. Let this be equal to F ftlb/lb of liquid. The energy balance may be completely represented by the following equation:

⇒ X_A +U2_A/2gc + P_AV_A  – F + w =  X_B +  P_BV_B

If density of liquid is ρ lb/ft³ then VA = l/pA and VB = l/pB

⇒ X_A +U2_A/2gc +P_A / ρ_A  – F + w =  X_B +U2_B/2gc +P_A / ρ_B

Bernoulli’s Theorem Application: 

• One of the most common everyday applications of Bernoulli’s principle is in air flight
• The main way that Bernoulli’s principle works in air flight has to do with the architecture of the wings of the plane.
• In an airplane wing, the top of the wing is somewhat curved, while the bottom of the wing is flat.

Bernoulli’s theorem states the “total energy of a liquid flowing from one point to another remains constant” It applies to non-compressible liquids

1. Airflight
2. Lift
3. Baseball
4. Drafy
5. Sailing

Flow Of Fluids Reynolds Number

The Reynolds number is the ratio of inertial forces to viscous forces within a fluid that is subjected to relative internal movement due to different fluid velocities. The Reynolds number quantifies the relative importance of these two types of forces for given flow conditions and is a guide to when turbulent flow will occur in a particular situation.

Reynolds number gives information about the flow of fluids and indicates whether its flow of fluid is laminar or turbulent.

• Laminar flow occurs at low Reynolds numbers, where viscous forces are dominant, and is characterized by smooth, constant fluid motion.
• Turbulent flow occurs at high Reynolds numbers and is dominated by inertial forces, which tend to produce chaotic eddies, vortices, and other flow instabilities.

If Re < 2100, flow is laminar.

For Re > 4000, flow is turbulent.

For 2100 < Re < 4000, flow- is in transition from laminar to turbulent

Reynolds number can be determined by using the following formula:

R = Inertial force/ viscous force

R = ρυD/μ

1. R is the Reynolds number
2. ρ is the fluid density in kilograms-per-cubic-meter (kg/m3).
3. v is the velocity in meters-per-second (m/s).
4. D is the diameter of the pipe in meters (m).
5. μ is the viscosity of the fluid in pascal-seconds (Pa s).
6. Reynolds number can also be expressed as

R = Inertial force/Viscous forces

= Mass  × Acceleration of liquid flowing / Shear stress ×  Area

Significance of Reynolds Number Applications:

1. Reynolds number plays an important part in the calculation of the friction factor in a few of the equations of fluid mechanics, including the Darcy-Weisbach equation
2. It is used when modeling the movement of organisms swimming through water.
3. Atmospheric air is considered to be a fluid. Hence, the Reynolds number can be calculated for it.
4. This makes it possible to apply it in wind tunnel testing to study the aerodynamic properties of various surfaces.
5. Reynolds number is used to predict the nature of flow during the experiment.
6. Turbulent flow chromatography is often used for on-line sample cleanup of biological matrices in liquid chromatography-mass spectrometry applications

Flow Of Fluids Energy Losses During Fluid Flow

When a fluid is flowing through a pipe, the fluid experiences some resistance due to which some of the energy of the fluid is lost. This loss of energy is classified as:

Major Energy Losses

1. Frictional Losses in Laminar Flow:
   • Darcy’s equation can be used to find head losses in pipes experiencing laminar flow by noting that for laminar flow,
   • The friction factor equals the constant 64 divided by the Reynolds number
   • f = 64/R_e
   • Substituting this into Darcy’s equation gives the Hagen-Poiseuille equation →  H_L = 64/ R_e [L/D][v₂/2g]
2. Frictional Losses in Turbulent Flow:
   • Darcy’s equation can be used to find head losses in pipes experiencing turbulent flow.
   • However, the friction factor in turbulent flow is a function of the Reynolds number and the relative roughness of the pipe.
3. Effect of Pipe Roughness:
   • The relative roughness of pipe is defined as the ratio of inside surface roughness (s) to the diameter
   • Relative roughness = ε/ D

Minor Energy Losses

The loss of energy due to a change of velocity of the flowing fluid in magnitude or direction is called minor loss of energy. The minor loss of energy includes the following cases:

1. Energy Losses in Bends and Fittings:

When the direction of flow is altered or distorted, as when the fluid is flowing round bends in the pipe or through fittings of varying cross-sections, energy losses occur which are not recovered.

• This energy is dissipated in eddies and additional turbulence and finally lost in the form of heat.
• However, this energy must be supplied if the fluid is to be maintained in motion, In the same way, as energy must be provided to overcome friction.
• Losses in fittings have been found, as might be expected, to be proportional to the velocity head of the fluid flowing.
• In some cases, the magnitude of the losses can be calculated but more often they are best found from tabulated values based largely on experimental results.
• The energy loss is expressed In the general form,

E_f = kV²/2

Where V is the velocity of the fluid, k has to be found for the particular fitting. Values of this constant k for some fittings are given in Table

Friction loss factors in fittings

Energy is also lost at sudden changes in pipe cross-section. At a sudden enlargement, the loss is equal to

⇒ E_f = (v₁-v₂)²/2

For a sudden contraction

E_f = kV²/2

Where v₁ is the velocity upstream of the change in section and v₁ is the velocity downstream of the change in pipe diameter from D₁ to D₂.

The coefficient k in the equation depends upon the ratio of the pipe diameters (D₂/D₁) as given in Table

Loss factors in contractions:

2. Sudden expansion of pipe:

The head due to the sudden expansion equation is the (V₁-V₂)/2g

Where V₁ is the velocity at the section  1

V₂ is the velocity in section 2

3. Sudden contraction of pipe:

The head loss due to the sudden contraction equation is

hc = k(V²₂/2g)

Where k= [(1/C_c)-1]²

V₂ is the velocity in section 2

Flow Of Fluids Measurement Of Rate

Pitot Tube

A Pitot tube, also known as a Pitot probe, is a pressure measurement instrument used to measure fluid flow velocity.

• The pitot tube was invented by the French engineer Henri Pitot in the early 18th century and was modified to its modern form in the mid-19th century by French scientist Henry Darcy.
• It is widely used to determine the airspeed of an aircraft, and the water speed of a boat, and to measure liquid, air, and gas flow velocities in certain industrial applications.
• The pitot tube is used to measure the local flow velocity at a given point in the flow stream and not the average flow velocity in the pipe.

Pitot Tube Construction:

It is a fluid velocity measuring instrument that can also be used for flow measurement of liquids and gases.

• It consists of two hollow tubes that sense pressure at different places within the pipe.
• These hollow tubes can be mounted separately in a pipe or installed together in one casing as a single device.
• One tube measures the. stagnation or impact pressure and another tube measures only static pressure usually at the wall of the pipe

Pitot Tube Principle:

When a solid body is kept centrally, and stationary in a pipeline with flowing fluid.

• The velocity of the fluid starts reducing (at the. same time the pressure fluid increases due to the conversion of kinetic energy into pressure energy) due to.
• Presence of the body. Directly in front of the solid body, the velocity becomes zero. This point is known as the stagnation point.
• The fluid flow can be measured by measuring the differences between the pressure at the normal flow line (static pressure) and the stagnation point (stagnation pressure).

Pitot Tube Working:

The liquid flows up the tube and when equilibrium is attained, the liquid reaches a height above the free surface of the water stream.

• Since the static pressure, under this situation, is equal to the hydrostatic pressure due to its depth below the free surface:
• The difference in level between the liquid in the glass tube and the free surface becomes the measure of dynamic pressure.

The equation of velocity is derived by applying Bernoulli’s principle; the final equation is given below:

Velocity , υ= \(\sqrt{(2gh)}\)

g = Acceleration due to gravity

Actual velocity = C_υ \(\sqrt{(2gh)}\)

Pitot Tubes Advantages:

• Economical to install.
• Does not contain moving parts; this minimizes the frictional loss.
• Easy to install due to its small size. It can introduce fluid flow without shutting down the flow.
• The loss of pressure is very small.
• Can be easily installed in extreme environments, high temperatures, and pressure conditions.

Pitot Tubes Disadvantages:

1.  Low sensitivity and poor accuracy. It requires high-velocity flow.
2. Not suitable for dirty or sticky fluid like sewage disposal.
3. Sensitivity disturbed by the flow direction
4. Pitot tubes have found limited applications in industries because they can easily become clogged with foreign materials in the liquid.
5. There is no standardization for pitot tubes.
   Change in velocity profile may cause significant errors. Due to a change in velocity profile, it develops a very low differential pressure which is difficult to measure.

Venturi meter

Venturi meter Principle:

A venturi meter is an example of a restriction-type flow meter.

• Its work is based on Bernoulli’s principle. In Venturimeter, Pressure energy (PE) is converted into Kinetic Energy (KE) to calculate the flow rate (discharge) in a closed pipeline.
• When a venturi meter is placed in a pipe carrying the fluid whose flow rate is to be measured, a pressure drop occurs between the entrance and the throat of the venturi meter.
• This pressure drop is measured using a differential pressure sensor and when calibrated this pressure drop becomes a measure of flow rate.

Venturi meter Construction:

Above the general dimensions of a Herschel standers type venturimeter.

It consists of three parts:

1. Converging inlet or inlet cone
2. Throat
3. Divergent cone or outlet cone.

Venturimeter is usually made of cast iron, bronze, or steel. The converging part is made shorter by employing a large cone angle (19° – 21°) while the diverging section is longer with a lower cone angle (5°-15°). The high-pressure tap is located at starting of the Venturi and the low-pressure tap is located in the middle of the throat sections. The accuracy of this type of flow meter ranges from ± 0.25% to ± 3%

Venturi meter Working:

The venturi meter is used to measure the rate of flow of fluid flowing through the pipes. Here we have considered two cross-sections, the first at the inlet and the second one at the throat.

• The difference in the pressure heads of these two sections is used to calculate the rate of flow through the venturimeter.
• As the water enters the inlet section i.e. in the converging part it converges and reaches the throat.
• The throat has a uniform cross-section area and the least cross-section area in the venturimeter.
• As the water enters the throat its velocity increases and due to an increase in the velocity the pressure drops to the minimum.
• Now there is a pressure difference of the fluid at the two sections.
• In section 1 (i.e. at the inlet) the pressure of the fluid is maximum and the velocity is minimum.
• In section 2 (at the throat) the velocity of the fluid is maximum and the pressure is minimum.
• The pressure difference at the two sections can be seen in the manometer attached at both sections.
• This pressure difference is used to calculate the rate flow of a fluid flowing through a pipe.

a₁, a₂ = Area of cross-section at inlet and throat.

g = Acceleration due to gravity

h = Pressure head difference

C_d = Coefficient of discharge

Venturi meter Uses:

• Venturimeter is used in a wide variety of applications that include gas, liquids, slurries,’ suspended oils, and other processes where the permanent pressure loss is not tolerable.
• It is widely used in large-diameter pipes such as found in the waste treatment process.
• It allows solid particles to flow through it because of their gradually sloping smooth design; so they are suitable for the measurement of dirty fluid.
• It also.is used to measure fluid velocity.

Venturi meter Advantages:

• High-pressure recovery. Low permanent pressure drop.
• High coefficient of discharge.
• Smooth construction and low cone angle help the solid particles flow through it.
• So it can be used for dirty fluids.
• It can be installed in any direction horizontal, vertical or inclined.
• More accurate than the orifice and flow nozzle.

Venturi meter Disadvantages :

1. Size as well as cost is high.
2. Difficult to inspect due to its construction.
3. Nonlinear.
4. For satisfactory operation, the venturi must be proceeded by long straight pipes.
5. Its maintenance is not easy.
6. It cannot be used in a pipe that has a small diameter (70mm).

 Orifice Meter

An Orifice Meter is a type of flow meter used to measure the rate of flow of liquid or gas, especially steam, using the Differential Pressure Measurement principle.

• It is mainly used for robust applications as it is known for its durability and is very economical.
• As the name implies, it consists of an Orifice plate which is the basic element of the instrument.
• When this Orifice plate is placed in a line, a differential pressure is developed across the Orifice plate.

This pressure drop is linear and is in direct proportion to the flow rate of the liquid or gas.

 Orifice Meter Principle:

• When a liquid/gas, whose flow rate is to be determined, is passed through an Orifice meter, there is a drop in the pressure between the INLET section and outlet section of the Orifice meter.
• This pressure drop can be measured using a differential pressure measuring instrument (The working principle of an Orifice meter is the same, as that of a venturi meter.)

Orifice Meter Construction:

 Orifice Meter Inlet:

• A linearly extending section of the same diameter as the inlet pipe for an end connection for an incoming flow connection.
• Here we measure the inlet pressure of the fluid/steam/gas.

Orifice plate:

• An Orifice Plate is inserted in between the Inlet and Outlet Sections to create a pressure drop and thus measure the flow.
• The Orifice plates in the Orifice meter in general, are made up of stainless steel of varying grades.

 Orifice Meter Outlet section:

A linearly extending section similar to the Inlet section. Here the diameter is the same as that of the outlet pipe for an end connection for an outgoing flow.

• Here we measure the pressure of the media at this discharge
• As shown in the adjacent diagram, a gasket is used to seal the space between the orifice plate and the flange surface, to prevent leakage.
• Sections 1 and 2 of the Orifice meter are provided with an opening for attaching a differential pressure sensor (u-tube manometer, differential pressure indicator).
• Orifice meters are built in different forms depending upon the application-specific requirement, the shape, size, and location of holes on the orifice plate

Describe the orifice meter specifications as per the following:

• Concentric orifice plate.
• Eccentric orifice plate.
• Segment orifice plate.
• Quadrant edge orifice plate.

 Orifice Meter Working:

The fluid flows inside the Inlet section of the Orifice meter having a pressure of P₁. As the fluid proceeds further into the converging section, its pressure reduces gradually and it finally reaches a value of P₂ at the end of the converging section and enters the cylindrical section.

• The differential pressure sensor connected between the inlet and the cylindrical throat section of the Orifice meter displays the pressure difference (P₁-P₂).
• This pressure difference is in direct proportion to the flow rate of the liquid flowing through the Orifice meter.
• Further, the fluid passes through the Diverging recovery cone section and the velocity reduces thereby regaining its pressure.
• Designing a lesser angle of the diverging recovery section helps more in regaining the kinetic energy of the liquid.

Orifice Meter Applications :

• Natural gas.
• Water treatment plants.
• Oil filtration plants.
• Petrochemicals and refineries.

Orifice Meter Advantages :

• The orifice meter is very cheap compared to other types of flow meters.
• Less space is required to install and hence ideal for space-constrained applications.
• The operational response can be designed with perfection.
• Installation direction possibilities: Vertical/Horizontal/Inclined.

Orifice Meter Disadvantages:

• Easily gets clogged due to impurities in gas or in unclear liquids.
• The minimum pressure that can be achieved for reading the flow is sometimes difficult to achieve due to limitations in the vena-contracta length for an orifice plate
• Unlike venturi meters, downstream pressure cannot be recovered in orifice meters.
• Overall head loss is around 40% to 90% of the differential pressure.
• Flow straighteners are required at the inlet and the outlet to attain streamlined flow thereby increasing the cost and space for installation.
• Orifice plates can get easily corroded with time thereby entailing an error.
• The discharge coefficient obtained is low.

Rotometer

• A rotometer is an example of a variable area meter.
• A variable area meter is a meter that measures fluid flow.
• Allowing the cross-sectional area of the device to vary in response to the flow causes some measurable effect that indicates the rate

Rotometer Construction and Working:

The rotometer consists of a gradually tapered tube; it is arranged in a vertical position.  The tube contains a float, which is used to indicate the flow of the fluid.

This float will be suspended in the fluid while fluid flows from the bottom of the tube to the top portion.

• The entire fluid will flow through the annular space between the tube and float.
• The float is the measuring element. The tube is marked with the divisions and the reading of the meter is obtained from the scale reading at the reading edge of the float.
• Here to convert the reading to the flow rate a calibration sheet is needed.
• For higher temperatures and pressure, where glass is not going to withstand, we use metallic tapered tubes.
• In metallic tubes, the float is not visible so we use a rod, which is called extension, which will be used as an indicator.
• Floats may be constructed using different types of materials from lead to aluminum glass or plastic.
• Stainless steel floats are common. According to the purpose of the meter, a float shape will be selected.

Rotometer Advantages :

• The pressure drop is constant.
• No special fuel or external energy is required to pump.
• Very easy to construct and we can use a wide variety of materials to construct.

Rotometer Disadvantages:

Due to its use of gravity, a rotometer must always be vertically oriented and right way up, with the fluid flowing upward.

• Due to its reliance on the ability of the fluid or gas to displace the float, graduations on a given rotometer will only be accurate for a given substance at a given temperature.
• The main property of importance is the density of the fluid; however, viscosity may also be significant.
• Floats are ideally designed to be insensitive to viscosity; however, this is seldom verifiable from manufacturers’ specifications.
• Either separate rotometers for different densities and viscosities may be used, or multiple scales on the same rotometer can be used.
• Rotometers normally require the use of glass (or other transparent material), otherwise the user cannot see the float.
• This limits their use in many industries to benign fluids, such as water.
• Rotometers are not easily adapted for reading by machine; although magnetic floats that drive a follower outside the tube are available.

Flow Of Fluids in Pharmaceutical Engineering Multiple Choice Questions

Question 1. A manometer is used to measure

1. Pressure in pipes
2. Atmospheric pressure
3. Very low pressures
4. Difference of pressure between two points

Answer: 3. Very low pressures

Question 2. A piezometer is used to measure

1. Pressure in pipes
2. Atmospheric pressure
3. Very low pressure
4. Difference of pressure between two points

Answer: 1. Pressure in pipes

Question 3. A differential manometer is used to measure

1. Pressure in pipes
2. Atmospheric pressure
3. Very low pressure
4. Difference of pressure between two points

Answer: 4. Difference of pressure between two points

Question  4. Which one of the following is known as fluid?

1. Always expands until it fills in the container
2. Cannot be subjected to shear, forces
3. Cannot remain at rest under the action of any shear forces
4. Practically compressible

Answer: 3. Cannot remain at rest under the action of any shear forces

Question  5. Which one of the following factors is responsible for the frictional factor, f, of a rough pipe and turbulent flow?

1. Relative roughness
2. Reynolds number
3. Reynolds number and Relative roughness
4. The size of the pipe and the discharge

Answer: 1. Relative roughness

Question 6. How many liquids are used in the differential manometer?

1. 3
2. 2
3. 4
4. 1

Answer: 2. 2

Question 7. Reynolds number is a ratio of the

1. Elastic forces to pressure forces
2. Gravity forces to inertial forces
3. Inertial forces to viscous forces
4. Viscous forces to inertial forces

Answer: 3. Inertial forces to viscous forces

Question 8. Which experiment is performed to study the flow of fluids?

1. Bernoulli’s
2. Orifice meter
3. Reynolds
4. Stokes

Answer: 1. Bernoulli’s

Question 9. The loss of head sudden enlargement in a pipe depends on one of the following differences

1. Diameters
2. Flow rates
3. Surface area
4. Viscosities

Answer: 3. Surface area

Question 10. Reynolds’ number depends on one of the following factors

1. Roughness of the pipe
2. Viscosity of the liquid
3. Surface area of the pipe
4. The volume of the liquid

Answer: 3. Surface area of the pipe

Distillation Pharmaceutical Engineering Introduction

Distillation is a process of separating the liquid components or substances from a liquid mixture by selective boiling and condensation at different places. Distillation may result in complete separation or it may be a partial separation that increases the concentration of selected components of the mixture.

The distillation process involves two steps:

1. Conversion of liquid into vapour phase.
2. Condensation of liquid at another place to recover the liquid.

The feed liquid is called as distill and the condensed liquid is known as distillate or condensate.

If one component is volatile and the other is nonvolatile, it is possible to separate volatile components from nonvolatile components by distillation (complete separation). In the case of two volatile components mixture, the highly volatile component gets vapourized at a lower temperature and then it is taken for condensation. In this case, the condensate contains a small amount of low volatile component (partial separation).

Difference between distillation and evaporation:

Distillation Pharmaceutical Engineering Applications

Makes up about 95% of all current industrial separation processes. It has been used in chemical industries, pharmaceutical and food industries, environmental technologies and petroleum refineries.

• The most common use is after a chemical reaction where we obtain some products. Distillation is used to separate the desired product from the rest obtaining a high purity product.
• Examples of the most important applications in, the food industry are. concentrating essential oils and flavours. The deodorization of fats and oils or in alcohol distillation.
• Some pharmaceutical processes based on the concentration of antibiotics are also related with distillation columns.
• Distillation is the main part of petroleum refineries. The crude oil which contains a . complex mixture of hydrocarbons is pumped into a huge distillation column to be separated by different temperatures.
• The solvents used for extraction from crude drugs need to be recovered to prevent contamination of the environment. So they are recovered by using distillation techniques.
• It can be used in the purification of solvents.
• It is used to purify the products which are obtained by extraction.
• It is used to recover expensive solvents used during the extraction process

Distillation Pharmaceutical Engineering Different Methods

1. Simple distillation
2. Flash distillation
3. Fractional distillation
4. Azeotropic distillation
5. Distillation under reduced pressure
6. Steam distillation
7. Molecular distillation
8.  Falling Film Molecular Still Or Wiped Film Molecular Still
9.  Centrifugal Molecular Still

1. Simple Distillation:

It is also called differential distillation. Simple distillation is a procedure by which two liquids with different boiling points can be separated. Simple distillation (the procedure outlined below) can be used effectively to separate liquids that have at least a degree difference in their boiling points.

As the liquid being distilled is heated, the vapours that form will be richest in the component of the mixture that boils at the lowest temperature.

• Purified compounds will boil, and thus turn into vapours, over a relatively small temperature range (2 or 3°C); by carefully watching the temperature in the distillation flask, it is possible to affect a reasonably good separation.
• As distillation progresses, the concentration of the lowest boiling component will steadily decrease.
• Eventually, the temperature within the apparatus will begin to change; a pure compound is no longer being distilled.
• The temperature will continue to increase until the boiling point of the next-lowest-boiling compound is approached.
• When the temperature again stabilizes, another pure fraction of the distillate can be collected. This fraction of distillate will be primarily the compound that boils at the second lowest temperature.
• This process can be repeated until all the fractions of the original mixture have been separated.

Simple Distillation Principle:

Liquid boils when its vapour pressure equals atmospheric pressure. Simple distillation is conducted at its boiling point. If the difference in volatility is greater then the separation becomes more easy and effective. When the liquid mixture is boiled it forms the vapour of volatile components. Then this vapour is condensed in another part of the distillation apparatus.

Simple Distillation Apparatus:

The construction of a simple distillation apparatus. It consists of a distillation flask with a side arm sloping downwards. The condenser is fitted into side arm using a cork. The condenser is usually a water condenser, that is jacketed for the circulation of water. The condenser is connected to the receiver flask using an adapter.

Simple Distillation Procedure:

1. Fill the distillation flask:
   • The flask should filled less than two-thirds because there needs to be sufficient clearance above the surface of the liquid so that when boiling starts the liquid should not enter into the condenser, which can affect the purity of the distillate.
   • Boiling chips should be placed in the distillation flask for two reasons: they will prevent superheating of the liquid being distilled and they will cause a more controlled boil, eliminating the possibility that the liquid in the distillation flask will bump into the condenser.
2.  Heat the distillation flask:
   • Heat the distillation flask slowly until the liquid begins to boil. Vapours will begin to rise through the neck of the distillation flask.
   • As the vapours pass through the condenser, they will condense and drip into the collection receiver.
   • An appropriate rate of distillation is approximately 20 drops per minute.
   • Distillation must occur slowly enough that all the vapours condense to liquid in the condenser.
   • Many organic compounds are flammable and if vapours pass through the condenser without condensing, they may ignite as they come in contact with the heat source..
   • (Note: All fractions of the distillate should be saved until it is shown that the desired compound has been effectively separated by distillation.)
3. Remove the heat source from the distillation flask:
   • Distillation flask before all of the liquid is vaporized.
   • If all of the liquid is distilled away, there is a danger that peroxides, which can ignite or explode, may be present in the residue left behind.
   • Also, when all of the liquid has evaporated, the temperature of the glass of the filtration flask will rise very rapidly, possibly igniting whatever vapours may still be present in the distillation flask.

Simple Distillation Applications:

• It is used for the preparation of distilled water and water for injection.
• Many volatile oils and aromatic waters are prepared by simple distillation.
• It is used in the purification of organic solvents.
• The concentration of liquid separates nonvolatile solids from volatile liquids such as alcohol and ether.

2.  Flash Distillation

Flash distillation is defined as a process in which an entire liquid mixture is suddenly vaporized (flash) by passing a feed from a high-pressure zone to a low-pressure zone.

• This process is frequently carried out as a continuous process and does not involve rectification.
• Flash distillation (sometimes called “equilibrium distillation”) is a single-stage separation technique.
• A liquid mixture feed is pumped through a heater to raise the temperature and enthalpy of the mixture.
• It then flows through a valve and the pressure is reduced, causing the liquid to partially vapourize. Once the mixture enters a enough big volume (The “flash drum’) the liquid and vapour separate.
• Because the vapour and liquid are in such close contact until the “flash” occurs the product liquid and vapour phases approach equilibrium.

Flash Distillation Principle:

• When a hot liquid mixture is allowed to enter from a high-pressure zone to a low-pressure zone, the entire mixture suddenly vaporizes.
• During this process, the chamber gets cooled because of a sudden drop in boiling point.
• Because of this cooling, the less volatile component condenses and is converted into liquid whereas the more volatile component remains in the vapour phase.
• The process requires the equilibrium to be reached and therefore the liquid and vapour are held in contact with each other for some time and then are separated.
• The liquid fraction is collected separately. The vapours are further condensed and collected.

Flash Distillation Construction and Working:

It consists of a pump which is connected to a feed reservoir. The pump helps in pumping the feed into a heating chamber which consists of a suitable heating mechanism. The other end of the pipe is directly introduced into the vapour liquid separator through a pressure-reducing valve.

A vapour outlet is provided at the top of the separator and a liquid outlet at the bottom. The feed is pumped through a heater at a certain pressure. The liquid gets heated and enters the vapour liquid separator through a pressure-reducing valve.

Due to the pressure drop the liquid flashes, which further enhances the vapourization process and there is flash boiling of the liquid mixture.

• But this sudden vaporization induces cooling.
• The vapour phase molecules of high boiling fraction get condensed while the low boiling fraction remains as vapour.
• The mixture is allowed to remain for a sufficient time so that vapour and liquid portions separate and achieve equilibrium.
• The liquid is collected from the bottom, while vapour from the top side is condensed further to achieve the second component in a liquid state.
• It can be used in the continuous mode by providing continuous feeding. The operating conditions can be adjusted in such a way that the amount of feed exactly equals the amount of material removed.

Flash Distillation Uses:

• Flash distillation is used for separating components, which boil at widely different temperatures.
• It is widely used in the petroleum industry for refining crude oil.

Flash Distillation Advantages:

• It is used for obtaining multicomponent systems of a narrow boiling range.
• It can be used in continuous mode.

Flash Distillation Disadvantages:

• Flash distillation is not suitable for the separation of components having comparable volatility.
• It is not suitable if the separated components are needed in pure quality.

3. Fractional Distillation

Fractional distillation is a process in which the vapourisation of a liquid mixture gives rise to a mixture of constituents from which the desired one is separated. This method is also called as rectification because a part of the vapour is condensed and returned as a liquid. This method is used to separate miscible volatile liquids whose boiling points are close.

Fractional Distillation Principle:

Fractional distillation is a mass transfer process involving counter-current diffusion of the component at each equilibrium stage.

• When a liquid mixture is distilled, the partial condensation of the vapour occurs at the fractionating column.
• In the column, the ascending vapour from the still is allowed to come in contact with the condensing vapour returning to the still.
• This results in the enrichment of the vapour with the more volatile component.
• By condensing the vapour and reheating the liquid repeatedly, equilibrium between liquid and vapour is set up at each stage, which ultimately results in the separation of the more volatile component.

Fractional Distillation Construction:

The apparatus is assembled as in The mixture is put into the round bottom flask along with a few anti-bumping granules (or a Teflon-coated magnetic stirrer bar if using magnetic stirring), and the fractionating column is fitted into the top. The fractional distillation column is set up with the heat source at the bottom of the still pot. As the distance from the still pot increases, a temperature gradient is formed in the column; it is coolest at the top and hottest at the bottom.

Fractional Distillation Working:

The process starts with taking a mixture of two liquids X and Y of which X is more volatile than Y. The mixture is taken in the distilling flask and is heated. The temperature rises slowly and the mixture begins boiling. Vapours will start forming. The vapours formed consist of more volatile component X with a small amount of less volatile component Y. Vapours start travelling in the fractionating column. Condensation of vapours of the less volatile liquid Y will start before those of the more volatile liquid X.

So by time, the vapours rising in the fractionating column will be more of X and the liquid flowing down will consist of liquid Y. The process of distillation and condensation is repeated. As a result of successive distillations, the vapours of more volatile component X will reach at the top, from there they are taken into the condenser and finally the substance is transferred to the container. Similarly, after a series of distillations, the remaining liquid in the distillation flask gets enriched in components with higher boiling points

Fractional Distillation Uses:

• One of the important uses of fractional distillation is to separate the crude oil into its various components such as gasoline, kerosene oil, diesel oil, paraffin wax, and liberating oil.
• Fractional distillation is also used for the purification of water.
• Water contains many dissolved impurities; these can be removed by this process.
• It is also used for separating acetone and water.
• Industrial use of fractional distillation is in petroleum refineries, chemical plants, natural gas processing and the separation of pure gases from mixture of gases.
• It has other industrial uses as it is used for the purification and separation of many organic compounds.

Fractional Distillation Disadvantage:

Fractional distillation cannot be used for miscible liquids.

4. Distillation under Reduced Pressure

Vacuum distillation is also called as distillation under reduced pressure. This technique is used for purifying or separating thermally unstable liquid compounds that decompose at their normal boiling points.

Distillation under Reduced Pressure Principle:

The lowering of pressure on the surface of a liquid (by using a vacuum) lowers its boiling point. As a result of this, a liquid can be boiled and distilled, without any decomposition, at a temperature much below its normal boiling point

Distillation under Reduced Pressure Equipment:

Distillation under reduced pressure or vacuum is carried out in a specially designed glass apparatus. A two-necked ‘Claisen’s flask’ is used, the main neck of which is fitted with a long capillary tube (capillary tube avoids bumping) and the side neck is fitted with a thermometer. The side tube is connected to a condenser carrying a receiver at the other end. The receiver is attached to a vacuum pump to reduce the pressure. The pressure is measured with the help of a manometer.

Distillation under Reduced Pressure Procedure:

The liquid is to be distilled is filled in the flask (one-half to two-thirds the volume of the flask). Small pieces of porcelain are added to the liquid to facilitate distillation and prevent bumping.

The capillary tube and thermometer are placed in the respective necks of the flask. The required vacuum is applied. The contents are heated gradually. The temperature rises and liquid gets vaporized rapidly due to the vacuum. The vapour passes through the condenser. The condensate is collected in the receiver.

Distillation under Reduced Pressure Advantages:

• The advantages of distillation under reduced pressure are:
• The compounds that decompose on heating to their boiling points can be purified by distillation under reduced pressure. This is because, at the reduced pressure, a liquid would boil at a temperature much below its normal boiling point.
•  Distillation under reduced pressure is more fuel-economical as it makes the liquid boil at temperatures well below the normal boiling point.
• The fractions are distilled off at relatively lower temperatures, cracking or decomposition being thus largely avoided.
•  In some crude drugs drying gives compact or dense residue which is undesirable. This method can produce a light porous mass due to the sudden evaporation of liquid.

Distillation under Reduced Pressure Disadvantages:

• In vacuum distillation, persistent foaming occurs.
• Not suitable for preparation of semisolid or solid extract.

5.  Steam Distillation

Steam distillation is a method in which steam is used for distillation and it is used for

• The separation of high boiling liquids from non-volatile impurities.
• The substances can get destroyed in high temperatures.

Liquids having high boiling points cannot be distilled by simple distillation, as the components of the mixtures may get degraded at high temperatures. In such cases, steam distillation is used.

Steam Distillation Principle:

When a mixture of two immiscible liquids

For example:

Water and Organics are heated and agitated, and the surface of each liquid exerts its vapour pressure as though the other component of the mixture was absent.

• Thus, the vapour pressure of the system increases as a function of temperature beyond what it would be if only one of the components was present.
• When the sum of the vapour pressures exceeds atmospheric pressure, boiling begins.
• Because the temperature of boiling is reduced, damage to heat-sensitive components is minimized.

Steam Distillation Assembly of apparatus:

The assembly of the apparatus for steam distillation on a laboratory scale.

• It consists of a metallic ‘steam can’ fitted with a cork having two holes. Through one of the holes, a long tube is passed to reach almost the bottom of the steam generator.
• This tube acts as a safety tube, so that in case the pressure inside the steam generator becomes too much, water will be forced out of it and the pressure will be relieved.
• Moreover, when steam starts coming out from the safety tube, it indicates that the steam can is almost empty. Through another hole, a bent tube is passed.

The other end of the bent tube is connected to the flask containing non-aqueous liquid

For example:

Crude containing Volatile oil through a rubber bung. This tube should reach almost the bottom of the flask.

• Through the other hole of the rubber bung, a delivery tube is inserted which connects the flask and the condenser.
• The condenser is connected to a receiver flask using an adaptor. Provisions are made to heat the steam can and flask.

Steam Distillation Procedure:

The non-aqueous liquid is placed in the flask. A small quantity of water is added to it. Steam can is filled with water. The steam generator and the flask are heated simultaneously so that a uniform flow of steam passes through the boiling mixture.

• The mixture gets heated.
• The steam carries the volatile oil and passes into the condenser, which is cooled by cold water.
• The condensed immiscible liquid is collected into the receiver.
• Distillation is continued until all the non-aqueous liquid has been distilled. In the receiver, water and organic liquid form two separate layers, which can be easily separated using a separating flask.
• For volatile substances, which are miscible with water, distillation with steam would involve the same principle of fractional distillation.

Steam Distillation Applications:

• Steam distillation is used for the separation of immiscible liquids.
• This method is used for extracting most of the volatile oils such as clove, anise and eucalyptus.
• It is useful in the purification of liquid with high boiling point.
• Camphor is distilled by this method.
• Aromatic waters are prepared by this method.

Steam Distillation Advantages:

• Volatile oils can be separated at a lower temperature in steam distillation, without any decomposition and loss of aroma.
• If a substance has low volatility, it can be satisfactorily distilled, provided its molecular weight is considerably higher than water.

Steam Distillation Disadvantage:

Steam distillation is not suitable when immiscible liquid and water react with each other.

6. Molecular Distillation

Molecular distillation is defined as the process in which each molecule in the vapour phase travels the mean free path and gets condensed individually without intermolecular collisions on the application of a vacuum.

Molecular Distillation Principle:

The mean free path is the average distance travelled by the molecule in a straight line without any collision. The mean free path is inversely proportional to number of molecules to 1 cc of the gaseous phase.

• That means the mean free path can be increased by reducing the number of molecules per cc.
• The process is carried out at a pressure as low as 1 μhg.
• The number of molecules is drastically reduced and if a molecule is being heated under such conditions or pressure, the molecule escapes from the evaporating surface and travels a few cm without colliding with residual gas in the space above.

If a condensing surface is placed within this distance a major fraction of the molecule is condensed and will not return back to the distillant. Residual gas offers negligible resistance to the evaporation.

• The energy supplied for distillation is solely utilized to evaporate the compound and no energy is dissipated in the collisions.
• Therefore for a given temperature molecular distillation takes place at a very high rate or for a given distillation rate molecular distillation operates at a quite low temperature because the distillation travelled by the molecules is very short.
• It is also called short-path distillation.
• The distillate molecules should get a chance to reach the evaporating surface and therefore the layer of the distillate should be thin to overcome the pressure of the layer above to come to the surface (hydrostatic head).
• Therefore the distillant is maintained in a thin layer i.e., turbulent to provide best chance to the molecules to reach the surface.
• Vapour is evolved from the surface only and therefore is also called as evaporative distillation.

Molecular Distillation Applications:

• Purification of chemicals such as tricresyl phosphate, dibutyl phthalate and dimethyl phthalate.
• More frequently used in the refining of fixed oils.
• Vitamin A is separated from fish liver oil. Vitamin E is concentrated by this from fish liver oils and other vegetable oils.
• Free fatty acids are distilled at 100°C. Steroids can be obtained between 100 ’C and 200”C, while triglycerides can be obtained from 200 °C onwards.
• Proteins and gums Will remain as nonvolatile residues. Thus, the above molecular distillation.

7. Falling Film Molecular Still or Wiped Film Molecular Still

Falling Film Molecular Stil Principle:

In this method, vaporisation occurs from a film of liquid flowing down a heated surface under a high vacuum. The vapour (molecules) travels a short distance and strikes the condenser nearby. Each molecule is condensed individually. The distillate is subsequently collected.

Falling Film Molecular Stil Construction:

This consists of a vessel. This vessel has a diameter of one meter. The walls of the vessel are provided with suitable means of heating (jacket). Wipers are provided adjacent to the vessel wall.  Wipers are connected to a rotating head through a rotor.

The condensers are arranged very close to the wall (evaporating surface).  The vacuum pump is connected to a large diameter pipe at the centre of the vessel. Provisions are made for collecting the distillate and the undistilled liquid residue at the bottom.

Falling Film Molecular Stil Working:

The vessel is heated by suitable means. Vacuum is applied at the centre of the vessel and wipers are allowed to rotate. The feed is entered through the inlet of the vessel.  As the liquid flows down the walls, it is spread to form a film by PTFE (polytetrafluoroethylene) wipers, which are moving at a rate of 3 metres per second.

The velocity of the film is 1.5 metres per second. Since the surface is already heated, the liquid film evaporates directly. The vapour (molecules) travels its mean free path and strikes the condenser.  The condensate is collected into a vessel. The residue (undistilled or mean free path not travelled) is collected from the bottom of the vessel and re-circulated through the feed port for further distillation. Capacity is about 1000 litres per hour.

8. Centrifugal Molecular Still

Centrifugal Molecular Still Principle:

In this method, liquid feed is introduced into a vessel, which is rotated at a very high speed (centrifugal action). On account of heating, vapourisation occurs from a film of liquid on the sides of the vessel. The vapour (molecules) travels a short distance and gets condensed on the adjacent condenser. Each molecule is condensed individually. The distillate is subsequently collected.

Centrifugal Molecular Still Construction:

It consists of a bucket-shaped vessel having a diameter of about 1 to 1.5 metres. It is rotated at high speed using 2 motors. Radiant heaters are provided externally to heat the fluid in the bucket. Condensers are arranged very close to the evaporating surface. The vacuum pump is connected to the entire vessel at the top. Provisions are made for introducing the feed into the centre of the bucket, for receiving the product and residue for re-circulation.

Centrifugal Molecular Still Working:

Vacuum is applied at the centre of the vessel. The bucket-shaped vessel is allowed to rotate at high speed. The feed is introduced from the centre of the vessel. Due to the centrifugal action of the rotating bucket, the liquid moves outward over the surface of the vessel and forms a film.

Since the radiant heaters heat the surface, the liquid evaporates directly from the film. The vapour (molecules) travels its mean free path and strikes the condenser. The condensate is collected into another vessel. The residue is collected from the bottom of the vessel and is recirculated through the feed port for further distillation.

Distillation Pharmaceutical Engineering Multiple Choice Questions

Question 1. Water for injection is prepared by using

1. Simple distillation
2. Fractional distillation
3. Molecular distillation
4. Steam distillation

Answer: 1. Simple distillation

Question 2. Which one of the methods is also called differential distillation?

1. Simple distillation
2. Molecular distillation
3. Fractional distillation
4. Steam distillation

Answer:  1. Simple distillation

Question 3. Which one of the following methods is used for distillation of camphor?

1. Fractional distillation
2. Steam distillation
3. Simple distillation
4. Molecular distillation

Answer:  4. Molecular distillation

Question 4. Which type of liquid evaporates first in the distillation process?

1. Immiscible liquid
2. Non-volatile liquid
3. Less volatile liquid
4. More volatile liquid

Answer: 4. More volatile liquid

Question 5. Which method we can use for the preparation of the aromatic spirit of ammonia?

1. Simple distillation
2. Molecular distillation
3. Fractional distillation
4. Steam distillation

Answer: 1. Simple distillation

Question 6. Which type of distillation is called as evaporative distillation?

1. Simple distillation
2. Fractional distillation
3. Molecular distillation
4. Steam distillation

Answer: 3. Molecular distillation

Question 7. Why condenser is placed in an inclined position?

1. Collect the condensate easily
2. Remove the film of condensed liquid
3. To use the gravity principle effectively
4. Fast condensation

Answer: 3. To use the gravity principle effectively

Question 8. Separation of liquid by distillation is based upon one of the following?

1. Boiling point
2. Miscibility
3. Viscosity
4. Vapour pressure

Answer: 3. Viscosity

Question 9. Mean free path is associated with

1. Simple distillation
2. Flash distillation
3. Molecular distillation
4. Steam distillation

Answer: 4. Steam distillation

Question 10. Complete separation of individual components is not possible in

1. Simple distillation
2. Molecular distillation
3. Fractional distillation
4. Steam distillation

‘Answer: 2. Molecular distillation

Evaporation In Pharmaceutical Engineering Introduction

Evaporation is the process of a substance in a liquid state changing to a gaseous state due to an increase in temperature and or pressure.

Or

Evaporation is a process in which large quantities of liquid are vaporized to get a concentrated product by applying heat.

• Evaporation is a type of vapourization that occurs on the surface of a liquid as it changes into the gaseous phase.
• The surrounding gas must not be saturated with the evaporating substance.
• When the molecules of the liquid collide, they transfer energy to each other based on how they collide.
• When a molecule near the surface absorbs enough energy to overcome the vapour pressure, it will “escape” and enter the surrounding air as a gas.
• When evaporation occurs, the energy removed from the vaporized liquid will reduce the temperature of the liquid, resulting in evaporative cooling.
• Either suspension or solutions can be subjected to evaporation.
• The only condition is that the liquid must be volatile and the solute must be nonvolatile. Since heat is supplied the constituents must be thermo-stable.

Evaporation In Pharmaceutical Engineering Objectives

• One of the primary objectives of this evaporation is to reduce the volume of the product by some significant amount without loss of nutrient components.
• To make transport and storage easier as evaporation decreases the weight and volume of the product.
• To remove large amounts of liquid from the product before the dehydration process.
• To improve the stability of the product.

Evaporation Applications In Pharmaceutical Engineering

• Manufacture of bulk drugs: The evaporation process is used in the manufacture of bulk drugs in pharmaceutical industries.
• It is also used in the formulation of biological products like enzymes, antibiotics, vitamins etc.
• In demineralization of water.
• Film deposition: Thin films may be deposited by evaporating a condensing it onto a substrate, or by dissolving the substance in a so vent, spreading the resulting solution thinly over a substrate and evaporating the solvent,
• Industrial applications include many printing and coating processes, recovering s<a\U from solutions.
• Concentration of blood plasma and serum.
• Removal of water and solvent from fermentation broths.
• Concentration of herbal extract.

Factors Influencing The Rate Of Evaporation In Pharmaceutical Engineering

1. Temperature:

• Temperature is directly proportional to the rate of evaporation. Increase in temperature increases the rate of evaporation.
• At a given temperature some molecules possess more kinetic energy than the other molecules. Fast-moving molecules will move from the surface to the vapour state.
• While the molecules having less kinetic energy will remain in the bulk of the liquid.
• If the temperature is increased the molecules will get more energy and they will escape from the surface of the liquid.

2. Vapour pressure:

• The rate is directly proportional to the vapour pressure of the liquid. If the vapour pressure of the liquid is more then the rate of evaporation will be more.
• The lower the external pressure the lower the boiling point of liquid and hence greater will be the evaporation.
• This condition is achieved by using a vacuum. Saturation of the overhead space with vapours of liquid decreases the evaporation rate.
• If the air already has a high concentration of the substance evaporating, then the given substance will evaporate more slowly.

3. Flow rate of air:

• This is in part related to the concentration points above.
• If “fresh” air (i.e., air which is neither already saturated with the substance nor with other substances) is moving over the substance all the time, then the concentration of the substance in the air is less likely to go up with time, thus encouraging faster evaporation.
• This is the result of the boundary layer at the evaporation surface decreasing with flow velocity, decreasing the diffusion distance in the stagnant layer.

5. Inter-molecular forces:

• The stronger the forces keeping the molecules together in the liquid state, the more energy one must get to escape.
• This is characterized by the enthalpy of vapourization.
• So stronger intermolecular forces will require high energy to evaporate the molecules. So the rate of evaporation will get decreased

6. Surface area:

A substance that has a larger surface area will evaporate faster, as there are molecules per unit of volume that are potentially able to escape. are more surface

7. Type of product required:

• The type of product which has to be evaporated decides the method of evaporation equipment for evaporation.
• This affects not only the rate of evaporation but also the quality of the final product, For example, an Open pan produces liquid or dry concentrate, which.
• The vacuum as well as the evaporator give the porous product.

8. Film and deposits:

• Some products during concentration form a film on the surface of the liquid.
• This film formed reduces the evaporating surface and precipitated matter (on the surface) hinders the transfer of heat.
• This can be avoided by stirring.

Differences Between Evaporation And Other Heat Processes In Pharmaceutical Engineering

1. Difference between Evaporation and Distillation: 

2. Difference between Evaporation and Sublimation:

3. Difference between Evaporation and Boiling:

4. Difference between Evaporation and Drying

5. Difference between Evaporation and Crystallization:

Equipment Used For Evaporation In Pharmaceutical Engineering

The equipment used for evaporation is called as evaporator.

They are classified as follows:

1. Evaporator with the heating medium in the jacket

Example:  Evaporating pan

2. Vapour-heated evaporators with tubular heating surfaces

1. Evaporators with tubes placed horizontally

Example: Horizontal tube evaporator

2. Evaporators with tubes placed vertically

1. Evaporators with short tubes
   1. Single effect evaporators
      • Example:  Short tube vertical evaporator
   2. Multiple effect evaporator
      • Example:  Triple effect evaporator
2. Evaporators with long tubes
   1. Evaporators with natural circulation
      • Example:  Climbing film evaporator (Rising film evaporator}
   2. Evaporators with forced circulation
      • Example:  Forced circulation evaporator

Steam Jacketed Kettle (Evaporating Pan) In Pharmaceutical Engineering

Evaporating pans or steam-jacketed kettles come under the classification of natural circulation evaporators.

It. consists of a hemispherical pan surrounded by a steam jacket. The hemispherical shape provides a large surface area for evaporation. The evaporation pan may be fixed and the emptying of the pan can be done from the product outlet.

 Steam-jacketed kettles Principle:

The conduction and convection mechanism is involved in the evaporation process. So that the heat is transferred by this mechanism to the material placed for evaporation in the pan. Steam provides heat to the pan in which the material is placed. The temperature rises and the escaping tendency of the solvent molecules into the vapour increases and enhances the vapourization of the solvent molecules.

 Steam-jacketed kettles Construction:

The construction of the steam-jacketed kettle or evaporating pan consists of two hemispherical pans one is the kettle (inner pan) and the other is called the jacket (outer).

• These two pans are joined to each other enclosing a space through which steam is passed. Several metals are used as materials for the construction of the kettle.
• Copper is an excellent material but it gets dissolved in acidic liquids to solve this problem tinned copper is used. Iron is used for the construction of the jacket because it has minimum conductivity.
• At the top of the jacket inlet for steam is provided.
• The jacket has two outlets one is for uncondensed gases (on the opposite side of the inlet) and another is to remove condensate (at the bottom of the jacket).
• The kettle is provided with one outlet for the product discharge at its bottom.

 Steam-jacketed kettles Working:

The liquid to be evaporated is poured into a kettle. Steam is provided from the steam inlet of the jacket.  This steam increases the temperature of the liquid. The condensed steam is removed from the outlet at the bottom of the jacket. The continuous stirring is essential.

To remove vapour to prevent condensation of liquid litres and also to accelerate the rate of evaporation fans are fitted.  A kettle of capacity up to about 90 litres may be made to tilt. The concentrated product is collected from the outlet of the kettle at the bottom.

 Steam-jacketed kettles Uses:

• An evaporating pan or steam-jacketed kettle is suitable for concentrating aqueous liquids.
• An evaporating pan or steam-jacketed kettle is suitable for concentrating thermo-stable liquors such as liquorice extracts.

 Steam-jacketed kettles Advantages:

• Evaporating pan or steam-jacketed kettle is constructed both for small scale and large scale batch operations.
• Evaporating pan or steam-jacketed kettle is simple in construction and easy to operate, clean and maintain.
• Its cost of installation and maintenance is low.
• For the construction of the evaporating pan. materials such as copper, stainless steel aluminium and so on a wide variety of materials can be used.
• Stirring of the contents or materials and removal of the products is easy.

 Steam-jacketed kettles Disadvantages:

• Decomposition of the product occurs which gets deposited at the bottom.
• The heating surface is limited and decreases proportionally to increase in the size of the pan.
• It is not suitable for the concentration of thermo-labile materials because the liquid is heated throughout in an open atmosphere. Further, there is evaporate under a reduced pressure
• The evaporating pan cannot be used
• For the evaporation of thermo-labelile pharmaceutical materials which are dissolved in an organic solvent, such as ethyl alcohol, as there is no provision to recollect the costly organic solvents.

Horizontal Tube Evaporator In Pharmaceutical Engineering

Horizontal Tube Evaporator Principle:

In this type of evaporator, the steam is passed through the horizontal tubes. These tubes are immersed in a liquid to be evaporated. Heat transfer takes place through the tubes and the liquid outside the tubes gets heated. These heated tubes provide heat to the liquid. The Iquid gets evaporated. The concentrated liquid is collected from the bottom.

Horizontal Tube Evaporator Construction:

It consists of a cylindrical body. The lower body ring is provided with a steam compartment closed on the outside with cover plates and inside by tube sheets. Between the tube sheets, several horizontal tubes is fastened. There are outlets for non-condensed gases and condensed steam. Feed enters at a convenient point and thick liquor is collected at the bottom.

The evaporator is usually made of cast iron. The average size of the body is 6 to 8 ft. in diameter- and 8 to 12 ft in height. The tube tank is shallower and its width is around half the diameter of the body.

The liquor level is carried slightly above the tubes. The babes are attached in a typical manner. A thick tube sheet is used, holes are bored a little larger in diameter than the diameter of the tubes and conical rubber gaskets are slipped into the tubes;o that tubes fit into the tube sheet.

Each set of 4 tubes is secured by drawing down a packing pate-held in place by a nut. Such an arrangement facilitates the removal of tubes. Tubes are long enough to project about 1/2″ beyond the tube sheet at either end

Horizontal Tube Evaporator Working:

Feed is introduced into the evaporator until the tubes are immersed. Steam is introduced into the steam compartment. Tubes receive heat from steam and conduct it to liquid. Steam condensate passes through the corresponding outlet. Feed receives heat and solvent gets evaporated. Vapour escapes through the outlet placed on the top. This process is continued until a thick liquid is formed which is collected from the outlet at the bottom.

Horizontal Tube Evaporator Use:

It is used for non-viscous solutions that do not deposit crystals on evaporation.

Horizontal Tube Evaporator Advantages:

• The cost of per square meter of heating surface is less in horizontal tube evaporator.
• It provides a more heating surface for evaporation.
• It requires less space for installation.
• It is cheap.

Horizontal Tube Evaporator Disadvantages:

• Liquid circulation is poor in this evaporator.
• The formation of a semisolid layer on the evaporating surface reduces heat transfer rates.
• Not suitable for viscous liquids.

Climbing Film Evaporator In Pharmaceutical Engineering

In a typical climbing film evaporator, the heat exchanger is mounted vertically and the evaporator liquid flows in an upward direction through the tubes. Water in the ev<iporator liquid boils as the liquid rises in the tubes. This boiling action helps force liquid up and out of the tubes. The liquid and vapour leave the heat exchanger together and enter the vapour body. After vapour separation, the evaporator liquid flows from the vapour body through the circulating pump to the heat exchanger.

Climbing film evaporator Principle:

In this evaporator, tubes are heated externally using steam. The liquid is to be evaporated is heated before entering these tubes. The liquid is then allowed to flow through these heated tubes. The liquid near the walls of heated tubes starts to evaporate by forming bubbles. These bubbles fuse and form larger bubbles, which travel up in the tubes. The liquid films are blown up from the top of the tubes and the strike entrainment separator (deflector) is kept above. This throws the liquid concentrate down into the lower part from where it is withdrawn.

Climbing film evaporator Construction:

In this evaporator, the heating unit consists of steam-jacketed tubes. Here, the tubes are held between two plates. An entrainment separator is placed at the top of the vapour head. The evaporator carries a steam inlet, vent outlet and condensate outlet. The feed inlet is from the bottom of the steam compartment

Climbing film evaporator Working:

The preheated liquid feed is entered from the bottom of the evaporator. Steam into the spaces around the tubes through the inlet. The temperature of the liquid increases due to the heated walls of the tubes. The liquid starts to evaporate as its temperature go on increasing.

The evaporated part of the liquid forms small bubbles. These bubbles unite to form bubbles of size equal to the size of the width of the tubes. These bubbles trap a part of the liquid (slug) when going upward through the tubes. As more vapour is formed, the slug of liquid is blown up in the tubes facilitating the liquid to spread as a film over the walls.

This film of liquid continues to vaporize rapidly. Finally, the mixture of liquid concentrate and vapour is ejected at a high velocity from the top of the tubes. The entrainment separator prevents entrainment as well as it breaks the foam. The vapour leaves from the top, while the concentrate is collected from the bottom.

Climbing film evaporator Uses:

• Using climbing film evaporator, thermo labile substances such as insulin, liver extracts and vitamins can be concentrated.
• Clear liquids, foaming liquids and corrosive solutions in large quantities can be operated.
• Deposit of scales can be removed quickly by increasing the feed rate or reducing the steam rate so that the product is unsaturated for a short time.

Climbing film evaporator Advantages:

• Long and narrow tubes provide a large surface area.
• Very high film velocity reduces boundary layers to a minimum giving improved heat transfer.
• The contact time between the liquid and the heating surface is very short. So, it is suitable for heat-sensitive materials.
• Unlike short tube evaporators, the tubes not submerged. So there is no elevation of boiling point due to hydrostatic head.
• It is suitable for foam-forming liquids because foam can be broken by an are entrainment separator.

Climbing film evaporator Disadvantages:

• Climbing film evaporator is expensive.
• Construction is quite complicated.
• It is difficult to clean and maintain.
• It is not advisable for very viscous liquids.

Forced Circulation Evaporator In Pharmaceutical Engineering

 Forced Circulation Evaporator Principle

In a forced circulation evaporator, the liquid is circulated through the tubes at high pressure using a pump. Hence boiling does not take place because the boiling point is elevated. Forced circulation of the liquids also creates some form of agitation. When the liquid leaves the tubes and enters the vapour head, the pressure falls suddenly. This lead to the flashing of super-heated liquor. Thus evaporation is affected.

 Forced Circulation Evaporator Construction and Working:

Any evaporator that uses a pump to ensure higher circulation velocity is called a forced circulation evaporator. Forced circulation evaporators are used if boiling of the product on the heating surfaces is to be avoided due to the fouling characteristics of the product, or to avoid crystallization. The flow velocity in the tubes must be high, and high-capacity pumps are required.

The liquid is typically heated only a few degrees for each pass through the heat exchanger, which means the recirculation flow rate has to be high. This type of evaporator is also used in crystallizing applications because no evaporation, and therefore no concentration increase, takes place on the heat transfer surface.

Evaporation occurs as the liquid is flash-evaporated in the separator/flash vessel. In’ crystallizer applications this is then where the crystals form, and special separator designs are used to separate crystals from the recirculated crystal slurry. The heat exchanger (in evaporator parlance sometimes called the “calandria”) can be arranged either horizontally or vertically depending on the specific requirements in each case

 Forced Circulation Evaporator Uses:

• If evaporation is conducted under reduced pressure, a forced circulation evaporator is suitable for thermo-labile substances.
• This method is used for the concentration of insulin and liver extracts.
• It is well suited for crystallizing operations where crystals are to be suspended at all times.

 Forced Circulation Evaporator Advantages:

• In a forced circulation evaporator, there is rapid liquid movement due to a high heat transfer coefficient.
• Salting, scaling and fouling are not possible due to forced circulation.
• This evaporator is suitable for labile substances because of rapid evaporation.
• It is suitable for viscous preparation because a pumping mechanism is used.

 Forced Circulation Evaporator Disadvantages:

• In a forced circulation evaporator the hold-up of liquids is high.
• The equipment is expensive because the power is required for the circulation of the liquids.

Multiple Effect Evaporator In Pharmaceutical Engineering

In single effect evaporator steam is used to heat the liquid which provides the latent heat ‘ of vapourization. The vapours are condensed in the condenser where the latent is given up to the cooling water and goes to waste.

To avoid this wastage two evaporators are connected with the piping arrangement so that the vapour from the calandria of the first effect is used to heat the calandria of the second effect. This means that the calandria of the second effect is used as a condenser for the first time.

So that the latent heat of vapourization is used to evaporate more quantity of the liquid instead of its going to waste. The vapour from the second effect is then taken to a condenser and converted into liquids. In general, not more than two or three effects are combined to have economical and efficient evaporation of liquids

Different types of feed arrangement of multiple effect evaporators:

1. Forward feed arrangement:

In this arrangement, the feed and steam introduced in the first effect and pressure in the first effect is highest and pressure in the last effect is minimum, so transfer of feed from one effect to another can be done without a pump.

2. Backward feed arrangement:

In this arrangement, feed is introduced in the last effect and steam is introduced in the first effect. For the transfer of feed, it requires a pump since the flow is from low pressure to higher pressure. Concentrated liquid is obtained in the first effect.

3. Mixed feed arrangement:

In this arrangement, feed is introduced in intermediate effect, flows in forward feed to the end of the series and is then pumped back to the first effect for final concentration. This permits the final evaporation to be done at the highest temperature.

Multiple Effect Evaporation In Pharmaceutical Engineering

Multiple Effect Evaporation Principle:

When the evaporator is fed with steam it boils the water present as feed. The water vapour produced has a large amount of heat which will go to waste if it is condensed. Therefore, in such case, evaporator makes very poor use of steam. The vapour used is suitable for passing to the calendria of the second evaporator where it is used as a heating medium.

If an evaporator is fed with steam at 126°C and it is evaporating water at 100°C then the water vapours coming off will also be at the temperature of 100° C and if these vapours are being used as the heating medium, water inside should boil at a lower temperature to maintain the temperature gradient for heat transfer. For this purpose vacuum should be drawn in the second evaporator to reduce the boiling point of water.

Multiple Effect Evaporation Construction:

The construction uses 3 evaporators i.e. Triple effect evaporator. The other aspects of the construction of the vertical tube evaporator remain the same. Vapour from first evaporator serves as the heating medium for the second and that from the second serves as a heating medium for the third evaporator. The last evaporator is connected to a vacuum pump

Multiple Effect Evaporation Working:

In the beginning, the multiple-effect evaporator is at room temperature and atmospheric pressure.

Liquid feed is introduced in all the 3 evaporators and the following operations are performed:

• Vent valves v₁, v₂, v₃ are open and other valves are closed.
• A vacuum is created in liquid chambers.
• Steam valve si and condensate valve Di are opened. Steam is supplied. Steam’ initially replaces cold air in the steam space of the first evaporator. When air is removed valve V₁ is closed.
• Steam is supplied till pressure P0 steam is created in steam space so that the temperature of the steam is t₀.
• Steam gives its temperature to liquid feed in the first evaporator and gets condensed.
• Condensate is removed through valve D₁.
• Liquid temperature increases and reaches boiling point ti, and vapour is generated exerting pressure p₁.
• This vapour displaces air in the upper part of the first evaporator and the steam space of the second evaporator.
• After the air is completely displaced from the steam space of the second evaporator, valve v₂ is closed.
• Vapour transmits heat t₁ to liquid in the second evaporator and gets condensed.
• Condensate is removed through valve D₂. Similar steps are continued in 3rd evaporator.

The steam to the first evaporator is at temperature t0 and pressure po. Feed is initially at room temperature. Steam gives its heat to feed. The difference in temperature of steam and feed reduces, Therefore the rate of condensation reduces. Therefore pressure in the vapour space of the first evaporator gradually increases to Pi. Increasing temperature to ti at which liquid boils in the first evaporator. The temperature gradient now is t₀– t₁.

The vapour from the first evaporator is now at a temperature ti and cannot boil the liquid in.

• For the second evaporator if its boiling point remains t₁ there will be no temperature gradient.
• In such case vacuum is drawn in the first evaporator so that liquid boils at t₂ and t₂ < t₂ so that the temperature gradient: of t₁– t₂ is maintained.
• The vapour in the first evaporator exerts pressure at P₂. Similar is the case with the third evaporator.
• As toiling proceeds liquid level in the first evaporator goes down. Feed is introduced through.
• The eed valve to maintain the liquid level constant. Similarly, feed is supplied to second and third-effect evaporators through valves F₂ and F₃.
• When the liquid in all three 3 evaporators is sufficiently concentrated, product valves are opened to collect the thick liquid.
• There is a continuous supply of steam and feed and a continuous withdrawal of products. The evaporator works continuously.

Multiple Effect Evaporation Uses:

• Vertical tube evaporator or short tube evaporator is used in the manufacture of the cascara extract.
• Vertical tube evaporator or short tube evaporator is used in the manufacture of salts
  and caustic soda.

Multiple Effect Evaporation Advantages:

• It is suitable for large-scale and continuous operation.
• It is highly economical when compared with a single effect.
• About 5 evaporators can be attached.

Economy of multiple effect evaporator:

The economy of the evaporator is the quantity of vapour produced per unit of steam admitted. It is calculated by considering the following assumptions. Feed is admitted at its boiling point. Therefore it does not require more heat to raise its temperature. Hence, the supplied steam gets condensed to give heat of condensation. This heat is then transferred to the liquid. The heat transferred now serves as latent heat of vapourization, i.e. Liquid undergoes vapourization by receiving heat. Loss of heat by any means is negligible.

The economy of the evaporator may be expressed as:

⇒ Economy of evaporator = Total mass of vapour produced/ Total mass of stem supplied

In a single effect, the evaporator stem is produced only once. Hence

⇒ The economy of a single effect evaporator = N units of vapour produced / N units of stem supplied = 1

In a multiple-effect evaporator, one unit of steam produces vapour many times, depending on the number of evaporators connected. Hence,

⇒ The economy of a multiple effect evaporator = N units of vapour produced/ 1 unit of stem supplied Not

So, the economy of the multiple effect evaporators is equal to the number of units connected multiplied by the economy of the single evaporator

Evaporation In Pharmaceutical Engineering Multiple-Choice Questions

Question 1. Which operation is generally carried out after evaporation?

1. Distillation
2. Crystallization
3. Extraction
4. Drying

Answer: 4. Drying

Question 2. Which condition should liquid fulfil to undergo the evaporation process?

1. Liquid should be volatile
2. Liquid should be viscous
3. Solent should not be volatile
4. Constituents must be heat-sensitive

Answer: 1. Liquid should be volatile

Question 3. What is the purpose of the entrainment separator in the climbing film evaporator?

1. Allowing the heat to transfer
2. Breaking the foam
3. Allowing the vapour to escape
4. Pulling the liquid up

Answer: 2. Breaking the foam

Question 4. Calendario consist of the number of

1. Baffles
2. Tubular surface
3. Outlets
4. Jackets

Answer: 2. Tubular surface

Question 5. What is the problem one can face during evaporation in climbing film evaporators?

1. Film formation
2. Droplet formation
3. Entrainment of liquid
4. The boiling point of liquid

Answer: 3. Entrainment of liquid

Question 6. Which evaporator gives the porous final product after evaporation?

1. Vacuum evaporator
2. Multiple effect evaporators
3. Pan Evaporator
4. Climbing film evaporator

Answer: 4. Climbing film evaporator

Question 7. Evaporation is carried out in which one of the following conditions?

1. At the boiling temperature
2. Room temperature
3. Above the boiling temperature
4. Below the boiling temperature

Answer: 3. Above the boiling temperature

Question 8. Which one of the following factors does not affect the evaporator?

1. Melting point of solids
2. The boiling point of liquids
3. Viscosity of liquid
4. Surface area of the evaporator

Answer: 1. Melting point of solids

Question 9. A triple-effect evaporator uses the concept of one of the following evaporators?

1. Vertical tube evaporator
2. Pan evaporator
3. Climbing film evaporator
4. Vacuum evaporator

Answer: 1. Vertical tube evaporator

Question 10. Feed is preheated in one of the following evaporators?

1. Climbing film evaporator
2. Pan evaporator
3. Vacuum evaporator
4. Forced circulation evaporator

Answer:  1. Climbing film evaporator

Size Separation Introduction

Size separation is a unit operation that involves the separation of particles of a particular size range from a mixture of different-sized particles. It is generally the step next to the size reduction. After size reduction particles prepared have wide size distribution. The narrow size distribution is necessary to confer equal physicochemical properties. It is necessary for pharmaceutical preparations like suspensions to avoid Ostwald ripening in tablets to form granules.

Official Standards For Powder Size

According to Indian pharmacopeia, the size of the powder is expressed by a mesh the aperture size of the sieve through which powder can pass.

I.P. categorizes powders as follows:

•  Coarse powders: A powder of which all the particles pass through a sieve with a nominal mesh aperture of 1.70 mm (No. 10 sieve) and not more than 40% through a sieve with a nominal mesh aperture of 355 pm (No. 44 sieve) is called coarse powder.
• Moderately coarse powder: A powder of which all the particles pass through a sieve with a nominal mesh aperture of 710 pm (No. 22 sieve) and not more than 40% through a sieve with a nominal mesh aperture of 250 pm (No. 60 sieve) is called moderately coarse powder.
• Moderately fine powder: If all particles of powder pass through a sieve with a nominal aperture of 355 pm (No. 44 sieve) and not more than 40% through a sieve with a nominal mesh aperture of 180 pm (No. 85 sieve) is called the moderately fine powder.
• Fine powder: If all the particles pass through a sieve with a nominal mesh aperture of 180 pm (No. 85 sieve) it is called a fine powder.
• Very fine powder: If all the particles pass through a sieve with a nominal mesh aperture of 125 pm (No. 120 sieve), it is called a very fine powder. In the United States Pharmacopoeia, powders are classified according to size as very coarse, coarse, moderately fine, fine, and very fine.

d₅₀ is the smallest sieve opening through which 50% or more of the material passes

Objectives Of Size Reduction

• To obtain powders of desired size distribution. Any solid material after size reduction gives particles of different sizes. So to get the particles of the desired size range one must go through the size separation.
• During tablet granulation the granules should be within a narrow size range, otherwise, weight variation will take place during tablet punching.
• To obtain a stable suspension. If the dispersed phase contains particles of a wide size range then they may increase the Ostwald ripening.
• To avoid the variations in physicochemical properties.
•  To set a quality control parameter for raw material.
• To improve mixing.

Applications Of Size Reduction Size Separation In Pharmaceutical Engineering

• Capsule filling: Uniform size particles are easy to fill in the capsules giving good flow properties.
• Tablet formulation: Uniform particle size ensures good flow from the hopper which avoids weight variation.
• It can serve as a quality control tool for the evaluation of raw materials.
• Removal of impurities based on size.
• Separation of solids from a gas suspension.
• Separation of coarse particles after levigation.
• Drugs that are intended for oral use should have a very small size (10 pm). So, much smaller-sized particles are separated by centrifugal classifiers.
• In the extraction process, the optimum size is needed to use for efficient extraction. For example, for extraction from Ashoka bark coarse powder is specified whereas for extraction from Rauwolfia root a moderately coarse powder is indicated.

Size Separation Sieves Size Separation In Pharmaceutical Engineering

A sieve is a surface having several apertures of specific dimensions.

• A material to be sieved is passed on the surface of the screen and agitated.
• The particles having a size less than the aperture size of the sieve are passed through the sieve where whereas the particles having a size more than the aperture are retained on the surface of the sieve.
• So, the particles of material get separated based on their size after sieving. By using sieves of different sizes the powder can be separated and graded.
• Sieves for pharmacopoeial testing are constructed from wire cloth with square meshes, woven from wires of brass, bronze, stainless steel, or any other suitable metal
• The wires should be of uniform circular cross-section and should not be coated or plated. Sieve metals should be compatible with the drugs to be screened.

Standards for Sieves

Sieves used for pharmacopoeial testing must specify the following:

• Number of sieves: The sieve number indicates the number of meshes in a length of 2.54 cm in each transverse direction parallel to the wires.
• Nominal size of aperture: Nominal size of aperture indicates the distance between the wires. It represents the length of the side of the square aperture. The I.P. has given the nominal mesh aperture size for the majority of sieves in mm or in μm.
• Nominal diameter of the wire: Wire mesh sieves are made from the wire having the specified diameter to give suitable aperture size and sufficient strength to avoid distortion of the sieve.
• Approximate percentage sieving area: This standard expresses the area of the meshes as a percentage of the total area of the sieve. It depends on the size of the wire used for any particular sieve number. Generally, the sieving area is kept within the range of 35 to 40 percent to give suitable strength to the sieve.
• Tolerance average aperture size: Some variation in the aperture size is unavoidable and when this variation is expressed as a percentage, it is known as the ‘aperture tolerance average’.
  • It is a limit given by pharmacopeia within which a particular dimension or average aperture size can be allowed to vary and still be acceptable for the purpose for which it is used.
  • Fine meshes cannot be woven with the same accuracy as coarse meshes.
  • Hence the aperture tolerance average is smaller for coarse sieves than the fine sieves.

Size Separation Mechanisms

Mechanical sieving devices are usually based on methods that agitate or brush the sieve or use centrifugal force.

1. Agitation: Sieves may be agitated in several different ways, for example:
   • Oscillation: The sieve is mounted in a frame that oscillates back and forth. The method is simple. The material may roll on the surface of the sieve, fibrous materials can form a ball of material.
   • Vibration: In this method, the sieve is vibrated at high speed electrically. The high speed of vibration is applied to the particles on the sieve. So the particles do not block the mesh.
   • Gyration: The gyratory method uses a system in which the sieve is on a rubber mounting and connected to an eccentric flywheel.
     • Thus, the sieve is given a rotary movement of small amplitude, but of considerable intensity, giving a spinning motion to the particles.
     • This increases the chances of a particle becoming suitably oriented to pass through the mesh so that the output is usually considered greater than that obtained with oscillating or vibratory sieves.
     • Agitation methods may be made continuous, by the inclination of the sieve and the provision of separate outlets for undersized and oversized particles.
     • This applies irrespective of the method of agitation.
2. Brushing: A brush can be used to move the particles on the surface of the sieve and to keep the meshes clear. A single brush across the diameter of an ordinary circular sieve, rotating about the mid-point is effective, but in large-scale production, a horizontal cylindrical sieve is employed, with a spiral brush rotating on the longitudinal axis of the sieve.
3. Centrifugal: A mechanical sieve of this type normally uses a vertical cylindrical sieve with a high-speed rotor inside the cylinder, so that particles are thrown outwards by centrifugal force. The current of air created by the movement assists sieving also, and is especially useful with very fine powders

Size Separation Instruments Size Separation In Pharmaceutical Engineering

1. Sieve Shaker

Sieve Shaker Principle:

The materials are separated based on their size due to high-speed vibratory motion. The finest particles are collected at the bottom sieve or the collecting pan and the particles having the largest size are collected in the upper sieve.

Sieve Shaker Construction:

In the sieve shaker, a set of sieves is used. These sieves are arranged in descending order i.e. sieve of a larger size is at the top and the sieve having the smallest size is placed at the bottom. The bottom sieve is attached to the receiving pan. The size separation is done by passing the powder through these sieves.

Sieve Shaker Working:

The powder is placed in the upper sieve. The sieves are shaken with the help of mechanical sieve shakers or electromagnetic devices. This motion helps the particles to pass through the sieve. After a particular period of shaking some weight of the powder is retained on each sieve depending on its size

Sieve Shaker Use:

It can be used for handling a variety of dry powders, granules, and dry foods.

Sieve Shaker Advantages:

• It requires less area for operation.
•  It is a fast and more accurate process.
• High speed of vibration avoids the blockage of the sieve.

Sieve Shaker Disadvantage:

Sieves should be used and stored with care, since if the sieve becomes damaged or distorted then it is of little value.

2. Cyclone Separator

Very low rates of separation are achieved if separation is done under the influence of gravitational force, especially at low velocities and low particle size. So, the separation can be enhanced by using centrifugal force. The cyclone separator works based on centrifugal force.

Cyclone Separator Principle:

In a cyclone separator, centrifugal force is used to separate solids from fluids. The separation process depends on particle size and particle density. It is also possible to allow fine- particles to be carried with the fluid.

Cyclone Separator Construction:

It consists of a short vertical, cylindrical vessel with a conical base. The upper part of the vessel is fitted with a tangential inlet The solid outlet is at the base. A fluid outlet is provided at the center of the top portion, which extends inwardly into the separator. Such an arrangement prevents the air from short-circuiting directly from the inlet to the outlet of the fluids.

Cyclone Separator Working:

The solids to be separated are suspended in a stream of fluid (usually air or water). Such feed is introduced tangentially at a very high velocity so that rotary movement takes place within the vessel. The centrifugal force throws the particles to the wall of the vessel. As the speed of the fluid (air) diminishes, the particles fall to the base and are collected at the solid outlet. The fluid (air) can escape from the central outlet at the top.

Cyclone Separator Advantages:

• Low capital cost.
• Relative simplicity and few maintenance problems.
• Low-pressure drop (ca. 2-6 w.c.).
• Dry collection and disposal.
• Relatively small space requirements.
• No moving parts.
• Can be used under extreme processing conditions.

Cyclone Separator Disadvantages:

• Offer low particulate collection efficiencies, especially for particulate sizes below 5 pm.
• Inability to handle sticky materials.

Cyclone Separator Uses:

• Cyclone separators are used to separate solid particles from gases.
• It is also used for size separation of solids in liquids.
• It is used to separate the heavy and coarse fractions from fine dust.
• It is used in oil refineries to separate oils and gases.

3. Air Separator

Air Separator Principle:

The cyclone separator alone cannot- carry out size separation on fine materials. For such separations, a current of air combined with centrifugal force is used. The finer particles are carried away by air and the coarse particles are thrown by centrifugal force, which fall at the bottom.

Air Separator Construction:

It consists of a cylindrical vessel with a conical base. A rotating plate is fitted on a shaft placed at the center of the vessel. A set of fan blades are also fitted with the same shaft.

At the base of the vessel, two outlets are provided:

1. One for the finer particles and
2. The other is for coarse particles.

Air Separator Working:

The disc and the fan are rotated using a motor. The feed (powder) enters at the center of the vessel and falls on the rotating plate. The rotating fan blades produce a draft (flow) of air in the direction. The fine particles are picked up by the draft of air and carried into the space of the settling chamber, where the air velocity is sufficiently reduced so that the fine particles are dropped and removed through the fine particle outlet. Particles too heavy to be picked up by the air stream are removed at the coarse particle outlet

Air Separator Uses:

Air separators are often attached to the ball mill or hammer mill to separate and return oversized particles for further size reduction

Air Separator Advantages

• It gives efficient separation in smaller apparatus.
• The waste does not interact with the generator of the airflow, avoiding wear and clogging.
• Low maintenance.
• High reliability.
• Low-pressure drop.

Air Separator Disadvantages

• Low separation yield.
• Unsuitable for separating smaller particles.

4. Filter Bag

Filter Bag Principle:

In filter bags, the separation of fine powder from coarse powder is carried out by applying suction. Firstly the mixture of powder which is to be separated is passed through a bag which is made up of cloth by applying suction at opposite side of the feeding. This causes the separation of fine and coarse powder. After this separation, the bags are shaken by giving pressure to remove the powder that is adhered to the bags. After that powder is collected from a conical base.

Filter Bag Construction:

It consists of several bags made of cotton or wool fabric. These are suspended in a metal container. A hopper is arranged at the bottom of the filter to receive the feed. At the top of the metal container, a provision is made for a vacuum fan and exhaust through the discharge manifold. At the top of the vessel, a bell-crank lever arrangement is made to change the action from filtering to shaking

Filter Bag Working: 

• Filtering period: During this period the vacuum fan produces a pressure lower than the atmospheric pressure within the vessel. Gas to be filtered enters the hopper, passes through the bags, and out of the top of the apparatus. The particles are retained within the bags.
• Shaking period: During this period the bell-crank lever first closes the discharge manifold and air enters through the top so the vacuum is broken. At the same time, it gives a violent jerking action to the bags so that they are freed from the dust. The fine particles are collected at the conical base.

Filter Bag Uses:

• Bag filters are used along with other size separation equipment, e.g. a cyclone separator.
• They are used on the top of a fluidized bed dryer for drying to separate the dust.
• They are used to clean the air of a room.
• The household vacuum cleaner is a simple version of a bag filter.

Filter Bag Advantages: 

• A bag filter is extremely useful for removing fines, which cannot be separated by other methods.
• These can be used to remove dust.
• Reduced sensitivity to particle size distribution.
• No high voltage requirements

Filter Bag Disadvantages:

• It has a high resistance which is about 600-1200 P.
• Fabric life may be substantially shortened in the presence of high-acid or alkaline atmospheres, especially at elevated temperatures.
• Collection of hygroscopic materials or condensation of moisture can lead to fabric plugging, loss of cleaning efficiency, and large pressure losses.

5. Elutriation Tank

Elutriation is a method of separation of particles based on their density. The smaller size particles have low density whereas the particles of larger size have more density. These particles are separated using a fluid flow.

Elutriation Tank Principle:

The separation in the elutriation tank is based on the density of the particles which depends on the size of the particles. After levigation, the material is kept in an elutriating tank and mixed with a large quantity of water. Then depending on the density of the particle it will either settle down or it will be suspended in water. Then the sample is collected at different heights.

Elutriation Tank Construction:

The apparatus consists of a vertical column with an inlet near the bottom of the suspension, an outlet at the base for coarse particles, and an overflow near the top of fluid and fine particles. One column will give a single separation into two fractions. If more than one step separation is required multiple tubes can be used in a serial connection.

Elutriation Tank Working:

The material which is to be separated is first legated. Then this paste or powder is kept in an elutriating tank and a large quantity of water is poured into the tank. The content of the tank is mixed with the water by stirring. The particles are uniformly distributed in the water. They are allowed to settle for some time.

The particles which are having large sizes (high density) will settle down and the particles with smaller sizes will remain suspended in the liquid. If the tank contains outlets at different heights then the multiple fractions can be separated by containing the particles of different size ranges. Then these fractions are dried to collect the powder.

Elutriation Tank Uses:

This technique is useful for separation of insoluble solids. These solids are first subjected to grinding and then elutriation.

Elutriation Tank Advantages:

• It is a continuous process.
• Several fractions can be collected by using columns of different areas.
• The separation is quick as compared to sedimentation.

Elutriation Tank Disadvantage:

Dilution of suspension may be undesirable in some cases

Size Separation Size Separation In Pharmaceutical Engineering Multiple Choice Questions

Question 1. Which one of the following indicates a nominal size of aperture?

1. Area of mesh as a percentage
2. Distance between two adjacent wires
3. Number of meshes per linear length
4. A wire having a specified diameter that gives a suitable aperture

Answer:  3. Number of meshes per linear length

Question 2. Size classification is also known as

1. Size separation
2. Size reduction
3. Size distribution
4. Size analysis

Answer: 1. Size Separation

Question 3. The brushing method enhances the movement of

1. Coarse materials
2. Light materials
3. Sticky materials
4. Crystalline materials

Answer:  3. Sticky materials

Question 4. In cyclone separator, the separation depends on

1. Density and shape
2. Shape and surface area
3. Size and density
4. Surface texture and size

Answer: 3. Size and density

Question 5. In the air separator centrifugal force for the circulation of air is supplied by

1. Applying vacuum
2. Atomizing air
3. Pumping
4. Rotating blades

Answer: 4. Rotating blades

Question 6. Which mechanism helps in size separation by the sieve shaker?

1. Centrifugal force
2. Sedimentation
3. Brushing
4. Shearing forces

Answer: 4. Shearing forces

Question 7. A screen that sharply separates the feed mixture is called as

1. Actual screen
2. Ideal screen
3. Virtual screen
4. Real screen

Answer: 4. Real screen

Question 8. The disadvantage of a sieve shaker is

1. Attrition
2. Capacity limited
3. Expensive equipment
4. Tedious

Answer: 2. Capacity limited

Question 9. The movement of particles can be enhanced during size separation by one of the following modes.

1. Agitation
2. Attrition
3. Gravitation
4. Mixing

Answer: 1. Agitation