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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