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Drying in Pharmaceutical Engineering Introduction

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

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

Moisture may be present in two forms in the product:

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

Drying in Pharmaceutical Engineering Objectives

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

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

Drying Applications in Pharmaceutical Engineering

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

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

Drying Process Mechanism in Pharmaceutical Engineering

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

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

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

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

Gravity flow theory and Vaporization and condensation mechanism

1. Diffusion Theory

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

The moisture movement takes place as follows:

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

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

Diffusion Limitations:

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

2. Capillarity Theory

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

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

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

3. Pressure Gradient Theory

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

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

Drying Methods in Pharmaceutical Engineering

The following are some general methods of drying:

Application of Hot Air (Convective or Direct Drying):

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

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

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

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

Dielectric drying:

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

Freeze Drying or Lyophilization:

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

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

Supercritical Drying (Superheated Steam Drying):

It involves steam drying of products containing water.

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

Natural Air Drying:

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

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

Equilibrium Moisture Content (EMC) in Pharmaceutical Engineering

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

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

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

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

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

Determination of Equilibrium Moisture Content:

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

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

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

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

EMC Application :

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

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

Drying Equipment in Pharmaceutical Engineering

There are. number of instruments available for drying purposes.

They are classified as follows:

1. based on the mechanism of drying:

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

2. Based on contact with material:

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

Tray Dryer in Pharmaceutical Engineering

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

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

Tray dryer Principle:

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

Tray dryer Construction:

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

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

Tray dryer Working:

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

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

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

Tray dryer Uses:

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

Tray dryer Advantages:

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

Tray dryer Disadvantages:

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

Drum Dryer in Pharmaceutical Engineering

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

Drum dryer Principle:

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

Drum dryer Construction:

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

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

Drum dryer Working:

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

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

Drum dryer Uses:

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

Drum dryer Advantages:

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

Drum dryer Disadvantages:

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

Spray Dryer in Pharmaceutical Engineering

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

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

Two types of atomizers are used, they are:

1. Jet atomizer
2. Rotary atomizer

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

Spray dryer Principle:

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

Spray dryer Construction:

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

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

Spray dryer Working:

Drying of the materials in the spray dryer involves three stages

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

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

Spray dryer of the liquid droplets:

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

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

Spray dryer Recovery of the dried products:

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

Spray dryer Uses:

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

Spray dryer Advantages:

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

Spray dryer Disadvantages:

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

Fluidized Bed Dryer in Pharmaceutical Engineering

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

 Fluid Bed Dryer Theory:

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

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

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

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

 Fluid bed dryer Principle:

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

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

 Fluid bed dryer Construction:

There are two types of fluidized bed dryers.

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

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

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

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

 Fluid bed dryer Working:

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

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

Fluid bed dryer Uses:

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

Fluid bed dryer Advantages:

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

Fluid bed dryer Disadvantages:

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

Vacuum Dryer in Pharmaceutical Engineering

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

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

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

 Vacuum dryer Principle:

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

 Vacuum dryer Construction:

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

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

Fluid bed dryer Working:

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

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

Fluid bed dryer Uses:

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

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

 Fluid bed dryer Advantages:

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

 Fluid bed dryer Disadvantages:

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

Freeze Drying in Pharmaceutical Engineering

Freeze drying Principle:

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

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

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

Freeze drying Equipment:

The equipment for freeze-drying consists of following parts

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

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

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

Freeze-drying process:

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

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

Freeze drying process involves the following steps:

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

1. Pretreatment:

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

2. Prefreezing:

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

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

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

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

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

3. Primary drying:

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

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

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

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

4. Secondary drying

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

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

5. Packing:

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

Freeze-drying Uses:

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

Freeze-drying Advantages:

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

Freeze-drying Disadvantages:

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

Drying in Pharmaceutical Engineering Multiple Choice Questions

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

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

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

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

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

Answer:  1. Air

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

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

Answer:  1. Atomizer

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

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

Answer:  4. Freeze drying

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

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

Answer:  3. Spray dryer

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

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

Answer: 1. Freeze drying

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

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

Answer: 1. Freeze dryer

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

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

Answer:  4. Freeze dryer

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

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

Answer:  1. The amount of liquid removed is less

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

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

Answer: 4. Zero

Flow Of Fluids in Pharmaceutical Engineering Introduction

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

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

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

Laminar flow and turbulent flow:

Flow Of Fluids Manometers

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

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

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

Manometer Classification 

Broadly manometers are classified into two classes

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

1. Inclined manometer

1. Piezometer:

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

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

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

The pressure at point A is given by:

⇒ p = wh,

Where w is the specific weight of the liquid.

Limitations of Piezometer:

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

2. U-tube manometer:

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

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

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

Characteristics of liquid used in U-tube Manometer:

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

U-tube Manometer Advantages:

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

U-tube Manometer Disadvantages:

• Fragile in construction
• Very sensitive to temperature changes

U-tube Manometer Applications:

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

3. Single-column manometer (micromanometer):

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

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

 Single Column Manometer Advantages:

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

Limitations of Single Column Manometer:

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

2. Differential manometer

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

Types of Differential Manometer:

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

U-tube Differential Manometer:

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

P_A – P_B = 9 x h (ρ_g – ρ₁)

Where

h = Difference in mercury level in the U-tube

ρ_g = Density of heavy liquid

ρ₁ = Density of liquid A

Inverted U-tube Differential Manometer:

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

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

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

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

ρ₁ = Density of liquid at A

ρ₂ = Density of liquid at B

ρ_g = Density of light liquid

h = Difference of light liquid

Where,

3. Inclined Type Manometer

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

Flow Of Fluids Bernoulli’s Theorem

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

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

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

Total energy = Potential energy + Kinetic energy + Pressure energy

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

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

⇒ X_B  +U2_B/2gc + P_BV_B

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

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

⇒ X_A +U2_B/2gc + P_BV_B + P_AV_A

= X_B  +U2_B/2gc + P_BV_B

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

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

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

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

Bernoulli’s Theorem Application: 

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

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

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

Flow Of Fluids Reynolds Number

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

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

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

If Re < 2100, flow is laminar.

For Re > 4000, flow is turbulent.

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

Reynolds number can be determined by using the following formula:

R = Inertial force/ viscous force

R = ρυD/μ

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

R = Inertial force/Viscous forces

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

Significance of Reynolds Number Applications:

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

Flow Of Fluids Energy Losses During Fluid Flow

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

Major Energy Losses

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

Minor Energy Losses

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

1. Energy Losses in Bends and Fittings:

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

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

E_f = kV²/2

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

Friction loss factors in fittings

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

⇒ E_f = (v₁-v₂)²/2

For a sudden contraction

E_f = kV²/2

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

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

Loss factors in contractions:

2. Sudden expansion of pipe:

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

Where V₁ is the velocity at the section  1

V₂ is the velocity in section 2

3. Sudden contraction of pipe:

The head loss due to the sudden contraction equation is

hc = k(V²₂/2g)

Where k= [(1/C_c)-1]²

V₂ is the velocity in section 2

Flow Of Fluids Measurement Of Rate

Pitot Tube

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

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

Pitot Tube Construction:

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

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

Pitot Tube Principle:

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

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

Pitot Tube Working:

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

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

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

Velocity , υ= \(\sqrt{(2gh)}\)

g = Acceleration due to gravity

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

Pitot Tubes Advantages:

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

Pitot Tubes Disadvantages:

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

Venturi meter

Venturi meter Principle:

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

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

Venturi meter Construction:

Above the general dimensions of a Herschel standers type venturimeter.

It consists of three parts:

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

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

Venturi meter Working:

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

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

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

g = Acceleration due to gravity

h = Pressure head difference

C_d = Coefficient of discharge

Venturi meter Uses:

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

Venturi meter Advantages:

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

Venturi meter Disadvantages :

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

 Orifice Meter

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

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

This pressure drop is linear and is in direct proportion to the flow rate of the liquid or gas.

 Orifice Meter Principle:

• When a liquid/gas, whose flow rate is to be determined, is passed through an Orifice meter, there is a drop in the pressure between the INLET section and outlet section of the Orifice meter.
• This pressure drop can be measured using a differential pressure measuring instrument (The working principle of an Orifice meter is the same, as that of a venturi meter.)

Orifice Meter Construction:

 Orifice Meter Inlet:

• A linearly extending section of the same diameter as the inlet pipe for an end connection for an incoming flow connection.
• Here we measure the inlet pressure of the fluid/steam/gas.

Orifice plate:

• An Orifice Plate is inserted in between the Inlet and Outlet Sections to create a pressure drop and thus measure the flow.
• The Orifice plates in the Orifice meter in general, are made up of stainless steel of varying grades.

 Orifice Meter Outlet section:

A linearly extending section similar to the Inlet section. Here the diameter is the same as that of the outlet pipe for an end connection for an outgoing flow.

• Here we measure the pressure of the media at this discharge
• As shown in the adjacent diagram, a gasket is used to seal the space between the orifice plate and the flange surface, to prevent leakage.
• Sections 1 and 2 of the Orifice meter are provided with an opening for attaching a differential pressure sensor (u-tube manometer, differential pressure indicator).
• Orifice meters are built in different forms depending upon the application-specific requirement, the shape, size, and location of holes on the orifice plate

Describe the orifice meter specifications as per the following:

• Concentric orifice plate.
• Eccentric orifice plate.
• Segment orifice plate.
• Quadrant edge orifice plate.

 Orifice Meter Working:

The fluid flows inside the Inlet section of the Orifice meter having a pressure of P₁. As the fluid proceeds further into the converging section, its pressure reduces gradually and it finally reaches a value of P₂ at the end of the converging section and enters the cylindrical section.

• The differential pressure sensor connected between the inlet and the cylindrical throat section of the Orifice meter displays the pressure difference (P₁-P₂).
• This pressure difference is in direct proportion to the flow rate of the liquid flowing through the Orifice meter.
• Further, the fluid passes through the Diverging recovery cone section and the velocity reduces thereby regaining its pressure.
• Designing a lesser angle of the diverging recovery section helps more in regaining the kinetic energy of the liquid.

Orifice Meter Applications :

• Natural gas.
• Water treatment plants.
• Oil filtration plants.
• Petrochemicals and refineries.

Orifice Meter Advantages :

• The orifice meter is very cheap compared to other types of flow meters.
• Less space is required to install and hence ideal for space-constrained applications.
• The operational response can be designed with perfection.
• Installation direction possibilities: Vertical/Horizontal/Inclined.

Orifice Meter Disadvantages:

• Easily gets clogged due to impurities in gas or in unclear liquids.
• The minimum pressure that can be achieved for reading the flow is sometimes difficult to achieve due to limitations in the vena-contracta length for an orifice plate
• Unlike venturi meters, downstream pressure cannot be recovered in orifice meters.
• Overall head loss is around 40% to 90% of the differential pressure.
• Flow straighteners are required at the inlet and the outlet to attain streamlined flow thereby increasing the cost and space for installation.
• Orifice plates can get easily corroded with time thereby entailing an error.
• The discharge coefficient obtained is low.

Rotometer

• A rotometer is an example of a variable area meter.
• A variable area meter is a meter that measures fluid flow.
• Allowing the cross-sectional area of the device to vary in response to the flow causes some measurable effect that indicates the rate

Rotometer Construction and Working:

The rotometer consists of a gradually tapered tube; it is arranged in a vertical position.  The tube contains a float, which is used to indicate the flow of the fluid.

This float will be suspended in the fluid while fluid flows from the bottom of the tube to the top portion.

• The entire fluid will flow through the annular space between the tube and float.
• The float is the measuring element. The tube is marked with the divisions and the reading of the meter is obtained from the scale reading at the reading edge of the float.
• Here to convert the reading to the flow rate a calibration sheet is needed.
• For higher temperatures and pressure, where glass is not going to withstand, we use metallic tapered tubes.
• In metallic tubes, the float is not visible so we use a rod, which is called extension, which will be used as an indicator.
• Floats may be constructed using different types of materials from lead to aluminum glass or plastic.
• Stainless steel floats are common. According to the purpose of the meter, a float shape will be selected.

Rotometer Advantages :

• The pressure drop is constant.
• No special fuel or external energy is required to pump.
• Very easy to construct and we can use a wide variety of materials to construct.

Rotometer Disadvantages:

Due to its use of gravity, a rotometer must always be vertically oriented and right way up, with the fluid flowing upward.

• Due to its reliance on the ability of the fluid or gas to displace the float, graduations on a given rotometer will only be accurate for a given substance at a given temperature.
• The main property of importance is the density of the fluid; however, viscosity may also be significant.
• Floats are ideally designed to be insensitive to viscosity; however, this is seldom verifiable from manufacturers’ specifications.
• Either separate rotometers for different densities and viscosities may be used, or multiple scales on the same rotometer can be used.
• Rotometers normally require the use of glass (or other transparent material), otherwise the user cannot see the float.
• This limits their use in many industries to benign fluids, such as water.
• Rotometers are not easily adapted for reading by machine; although magnetic floats that drive a follower outside the tube are available.

Flow Of Fluids in Pharmaceutical Engineering Multiple Choice Questions

Question 1. A manometer is used to measure

1. Pressure in pipes
2. Atmospheric pressure
3. Very low pressures
4. Difference of pressure between two points

Answer: 3. Very low pressures

Question 2. A piezometer is used to measure

1. Pressure in pipes
2. Atmospheric pressure
3. Very low pressure
4. Difference of pressure between two points

Answer: 1. Pressure in pipes

Question 3. A differential manometer is used to measure

1. Pressure in pipes
2. Atmospheric pressure
3. Very low pressure
4. Difference of pressure between two points

Answer: 4. Difference of pressure between two points

Question  4. Which one of the following is known as fluid?

1. Always expands until it fills in the container
2. Cannot be subjected to shear, forces
3. Cannot remain at rest under the action of any shear forces
4. Practically compressible

Answer: 3. Cannot remain at rest under the action of any shear forces

Question  5. Which one of the following factors is responsible for the frictional factor, f, of a rough pipe and turbulent flow?

1. Relative roughness
2. Reynolds number
3. Reynolds number and Relative roughness
4. The size of the pipe and the discharge

Answer: 1. Relative roughness

Question 6. How many liquids are used in the differential manometer?

1. 3
2. 2
3. 4
4. 1

Answer: 2. 2

Question 7. Reynolds number is a ratio of the

1. Elastic forces to pressure forces
2. Gravity forces to inertial forces
3. Inertial forces to viscous forces
4. Viscous forces to inertial forces

Answer: 3. Inertial forces to viscous forces

Question 8. Which experiment is performed to study the flow of fluids?

1. Bernoulli’s
2. Orifice meter
3. Reynolds
4. Stokes

Answer: 1. Bernoulli’s

Question 9. The loss of head sudden enlargement in a pipe depends on one of the following differences

1. Diameters
2. Flow rates
3. Surface area
4. Viscosities

Answer: 3. Surface area

Question 10. Reynolds’ number depends on one of the following factors

1. Roughness of the pipe
2. Viscosity of the liquid
3. Surface area of the pipe
4. The volume of the liquid

Answer: 3. Surface area of the pipe

Distillation Pharmaceutical Engineering Introduction

Distillation is a process of separating the liquid components or substances from a liquid mixture by selective boiling and condensation at different places. Distillation may result in complete separation or it may be a partial separation that increases the concentration of selected components of the mixture.

The distillation process involves two steps:

1. Conversion of liquid into vapour phase.
2. Condensation of liquid at another place to recover the liquid.

The feed liquid is called as distill and the condensed liquid is known as distillate or condensate.

If one component is volatile and the other is nonvolatile, it is possible to separate volatile components from nonvolatile components by distillation (complete separation). In the case of two volatile components mixture, the highly volatile component gets vapourized at a lower temperature and then it is taken for condensation. In this case, the condensate contains a small amount of low volatile component (partial separation).

Difference between distillation and evaporation:

Distillation Pharmaceutical Engineering Applications

Makes up about 95% of all current industrial separation processes. It has been used in chemical industries, pharmaceutical and food industries, environmental technologies and petroleum refineries.

• The most common use is after a chemical reaction where we obtain some products. Distillation is used to separate the desired product from the rest obtaining a high purity product.
• Examples of the most important applications in, the food industry are. concentrating essential oils and flavours. The deodorization of fats and oils or in alcohol distillation.
• Some pharmaceutical processes based on the concentration of antibiotics are also related with distillation columns.
• Distillation is the main part of petroleum refineries. The crude oil which contains a . complex mixture of hydrocarbons is pumped into a huge distillation column to be separated by different temperatures.
• The solvents used for extraction from crude drugs need to be recovered to prevent contamination of the environment. So they are recovered by using distillation techniques.
• It can be used in the purification of solvents.
• It is used to purify the products which are obtained by extraction.
• It is used to recover expensive solvents used during the extraction process

Distillation Pharmaceutical Engineering Different Methods

1. Simple distillation
2. Flash distillation
3. Fractional distillation
4. Azeotropic distillation
5. Distillation under reduced pressure
6. Steam distillation
7. Molecular distillation
8.  Falling Film Molecular Still Or Wiped Film Molecular Still
9.  Centrifugal Molecular Still

1. Simple Distillation:

It is also called differential distillation. Simple distillation is a procedure by which two liquids with different boiling points can be separated. Simple distillation (the procedure outlined below) can be used effectively to separate liquids that have at least a degree difference in their boiling points.

As the liquid being distilled is heated, the vapours that form will be richest in the component of the mixture that boils at the lowest temperature.

• Purified compounds will boil, and thus turn into vapours, over a relatively small temperature range (2 or 3°C); by carefully watching the temperature in the distillation flask, it is possible to affect a reasonably good separation.
• As distillation progresses, the concentration of the lowest boiling component will steadily decrease.
• Eventually, the temperature within the apparatus will begin to change; a pure compound is no longer being distilled.
• The temperature will continue to increase until the boiling point of the next-lowest-boiling compound is approached.
• When the temperature again stabilizes, another pure fraction of the distillate can be collected. This fraction of distillate will be primarily the compound that boils at the second lowest temperature.
• This process can be repeated until all the fractions of the original mixture have been separated.

Simple Distillation Principle:

Liquid boils when its vapour pressure equals atmospheric pressure. Simple distillation is conducted at its boiling point. If the difference in volatility is greater then the separation becomes more easy and effective. When the liquid mixture is boiled it forms the vapour of volatile components. Then this vapour is condensed in another part of the distillation apparatus.

Simple Distillation Apparatus:

The construction of a simple distillation apparatus. It consists of a distillation flask with a side arm sloping downwards. The condenser is fitted into side arm using a cork. The condenser is usually a water condenser, that is jacketed for the circulation of water. The condenser is connected to the receiver flask using an adapter.

Simple Distillation Procedure:

1. Fill the distillation flask:
   • The flask should filled less than two-thirds because there needs to be sufficient clearance above the surface of the liquid so that when boiling starts the liquid should not enter into the condenser, which can affect the purity of the distillate.
   • Boiling chips should be placed in the distillation flask for two reasons: they will prevent superheating of the liquid being distilled and they will cause a more controlled boil, eliminating the possibility that the liquid in the distillation flask will bump into the condenser.
2.  Heat the distillation flask:
   • Heat the distillation flask slowly until the liquid begins to boil. Vapours will begin to rise through the neck of the distillation flask.
   • As the vapours pass through the condenser, they will condense and drip into the collection receiver.
   • An appropriate rate of distillation is approximately 20 drops per minute.
   • Distillation must occur slowly enough that all the vapours condense to liquid in the condenser.
   • Many organic compounds are flammable and if vapours pass through the condenser without condensing, they may ignite as they come in contact with the heat source..
   • (Note: All fractions of the distillate should be saved until it is shown that the desired compound has been effectively separated by distillation.)
3. Remove the heat source from the distillation flask:
   • Distillation flask before all of the liquid is vaporized.
   • If all of the liquid is distilled away, there is a danger that peroxides, which can ignite or explode, may be present in the residue left behind.
   • Also, when all of the liquid has evaporated, the temperature of the glass of the filtration flask will rise very rapidly, possibly igniting whatever vapours may still be present in the distillation flask.

Simple Distillation Applications:

• It is used for the preparation of distilled water and water for injection.
• Many volatile oils and aromatic waters are prepared by simple distillation.
• It is used in the purification of organic solvents.
• The concentration of liquid separates nonvolatile solids from volatile liquids such as alcohol and ether.

2.  Flash Distillation

Flash distillation is defined as a process in which an entire liquid mixture is suddenly vaporized (flash) by passing a feed from a high-pressure zone to a low-pressure zone.

• This process is frequently carried out as a continuous process and does not involve rectification.
• Flash distillation (sometimes called “equilibrium distillation”) is a single-stage separation technique.
• A liquid mixture feed is pumped through a heater to raise the temperature and enthalpy of the mixture.
• It then flows through a valve and the pressure is reduced, causing the liquid to partially vapourize. Once the mixture enters a enough big volume (The “flash drum’) the liquid and vapour separate.
• Because the vapour and liquid are in such close contact until the “flash” occurs the product liquid and vapour phases approach equilibrium.

Flash Distillation Principle:

• When a hot liquid mixture is allowed to enter from a high-pressure zone to a low-pressure zone, the entire mixture suddenly vaporizes.
• During this process, the chamber gets cooled because of a sudden drop in boiling point.
• Because of this cooling, the less volatile component condenses and is converted into liquid whereas the more volatile component remains in the vapour phase.
• The process requires the equilibrium to be reached and therefore the liquid and vapour are held in contact with each other for some time and then are separated.
• The liquid fraction is collected separately. The vapours are further condensed and collected.

Flash Distillation Construction and Working:

It consists of a pump which is connected to a feed reservoir. The pump helps in pumping the feed into a heating chamber which consists of a suitable heating mechanism. The other end of the pipe is directly introduced into the vapour liquid separator through a pressure-reducing valve.

A vapour outlet is provided at the top of the separator and a liquid outlet at the bottom. The feed is pumped through a heater at a certain pressure. The liquid gets heated and enters the vapour liquid separator through a pressure-reducing valve.

Due to the pressure drop the liquid flashes, which further enhances the vapourization process and there is flash boiling of the liquid mixture.

• But this sudden vaporization induces cooling.
• The vapour phase molecules of high boiling fraction get condensed while the low boiling fraction remains as vapour.
• The mixture is allowed to remain for a sufficient time so that vapour and liquid portions separate and achieve equilibrium.
• The liquid is collected from the bottom, while vapour from the top side is condensed further to achieve the second component in a liquid state.
• It can be used in the continuous mode by providing continuous feeding. The operating conditions can be adjusted in such a way that the amount of feed exactly equals the amount of material removed.

Flash Distillation Uses:

• Flash distillation is used for separating components, which boil at widely different temperatures.
• It is widely used in the petroleum industry for refining crude oil.

Flash Distillation Advantages:

• It is used for obtaining multicomponent systems of a narrow boiling range.
• It can be used in continuous mode.

Flash Distillation Disadvantages:

• Flash distillation is not suitable for the separation of components having comparable volatility.
• It is not suitable if the separated components are needed in pure quality.

3. Fractional Distillation

Fractional distillation is a process in which the vapourisation of a liquid mixture gives rise to a mixture of constituents from which the desired one is separated. This method is also called as rectification because a part of the vapour is condensed and returned as a liquid. This method is used to separate miscible volatile liquids whose boiling points are close.

Fractional Distillation Principle:

Fractional distillation is a mass transfer process involving counter-current diffusion of the component at each equilibrium stage.

• When a liquid mixture is distilled, the partial condensation of the vapour occurs at the fractionating column.
• In the column, the ascending vapour from the still is allowed to come in contact with the condensing vapour returning to the still.
• This results in the enrichment of the vapour with the more volatile component.
• By condensing the vapour and reheating the liquid repeatedly, equilibrium between liquid and vapour is set up at each stage, which ultimately results in the separation of the more volatile component.

Fractional Distillation Construction:

The apparatus is assembled as in The mixture is put into the round bottom flask along with a few anti-bumping granules (or a Teflon-coated magnetic stirrer bar if using magnetic stirring), and the fractionating column is fitted into the top. The fractional distillation column is set up with the heat source at the bottom of the still pot. As the distance from the still pot increases, a temperature gradient is formed in the column; it is coolest at the top and hottest at the bottom.

Fractional Distillation Working:

The process starts with taking a mixture of two liquids X and Y of which X is more volatile than Y. The mixture is taken in the distilling flask and is heated. The temperature rises slowly and the mixture begins boiling. Vapours will start forming. The vapours formed consist of more volatile component X with a small amount of less volatile component Y. Vapours start travelling in the fractionating column. Condensation of vapours of the less volatile liquid Y will start before those of the more volatile liquid X.

So by time, the vapours rising in the fractionating column will be more of X and the liquid flowing down will consist of liquid Y. The process of distillation and condensation is repeated. As a result of successive distillations, the vapours of more volatile component X will reach at the top, from there they are taken into the condenser and finally the substance is transferred to the container. Similarly, after a series of distillations, the remaining liquid in the distillation flask gets enriched in components with higher boiling points

Fractional Distillation Uses:

• One of the important uses of fractional distillation is to separate the crude oil into its various components such as gasoline, kerosene oil, diesel oil, paraffin wax, and liberating oil.
• Fractional distillation is also used for the purification of water.
• Water contains many dissolved impurities; these can be removed by this process.
• It is also used for separating acetone and water.
• Industrial use of fractional distillation is in petroleum refineries, chemical plants, natural gas processing and the separation of pure gases from mixture of gases.
• It has other industrial uses as it is used for the purification and separation of many organic compounds.

Fractional Distillation Disadvantage:

Fractional distillation cannot be used for miscible liquids.

4. Distillation under Reduced Pressure

Vacuum distillation is also called as distillation under reduced pressure. This technique is used for purifying or separating thermally unstable liquid compounds that decompose at their normal boiling points.

Distillation under Reduced Pressure Principle:

The lowering of pressure on the surface of a liquid (by using a vacuum) lowers its boiling point. As a result of this, a liquid can be boiled and distilled, without any decomposition, at a temperature much below its normal boiling point

Distillation under Reduced Pressure Equipment:

Distillation under reduced pressure or vacuum is carried out in a specially designed glass apparatus. A two-necked ‘Claisen’s flask’ is used, the main neck of which is fitted with a long capillary tube (capillary tube avoids bumping) and the side neck is fitted with a thermometer. The side tube is connected to a condenser carrying a receiver at the other end. The receiver is attached to a vacuum pump to reduce the pressure. The pressure is measured with the help of a manometer.

Distillation under Reduced Pressure Procedure:

The liquid is to be distilled is filled in the flask (one-half to two-thirds the volume of the flask). Small pieces of porcelain are added to the liquid to facilitate distillation and prevent bumping.

The capillary tube and thermometer are placed in the respective necks of the flask. The required vacuum is applied. The contents are heated gradually. The temperature rises and liquid gets vaporized rapidly due to the vacuum. The vapour passes through the condenser. The condensate is collected in the receiver.

Distillation under Reduced Pressure Advantages:

• The advantages of distillation under reduced pressure are:
• The compounds that decompose on heating to their boiling points can be purified by distillation under reduced pressure. This is because, at the reduced pressure, a liquid would boil at a temperature much below its normal boiling point.
•  Distillation under reduced pressure is more fuel-economical as it makes the liquid boil at temperatures well below the normal boiling point.
• The fractions are distilled off at relatively lower temperatures, cracking or decomposition being thus largely avoided.
•  In some crude drugs drying gives compact or dense residue which is undesirable. This method can produce a light porous mass due to the sudden evaporation of liquid.

Distillation under Reduced Pressure Disadvantages:

• In vacuum distillation, persistent foaming occurs.
• Not suitable for preparation of semisolid or solid extract.

5.  Steam Distillation

Steam distillation is a method in which steam is used for distillation and it is used for

• The separation of high boiling liquids from non-volatile impurities.
• The substances can get destroyed in high temperatures.

Liquids having high boiling points cannot be distilled by simple distillation, as the components of the mixtures may get degraded at high temperatures. In such cases, steam distillation is used.

Steam Distillation Principle:

When a mixture of two immiscible liquids

For example:

Water and Organics are heated and agitated, and the surface of each liquid exerts its vapour pressure as though the other component of the mixture was absent.

• Thus, the vapour pressure of the system increases as a function of temperature beyond what it would be if only one of the components was present.
• When the sum of the vapour pressures exceeds atmospheric pressure, boiling begins.
• Because the temperature of boiling is reduced, damage to heat-sensitive components is minimized.

Steam Distillation Assembly of apparatus:

The assembly of the apparatus for steam distillation on a laboratory scale.

• It consists of a metallic ‘steam can’ fitted with a cork having two holes. Through one of the holes, a long tube is passed to reach almost the bottom of the steam generator.
• This tube acts as a safety tube, so that in case the pressure inside the steam generator becomes too much, water will be forced out of it and the pressure will be relieved.
• Moreover, when steam starts coming out from the safety tube, it indicates that the steam can is almost empty. Through another hole, a bent tube is passed.

The other end of the bent tube is connected to the flask containing non-aqueous liquid

For example:

Crude containing Volatile oil through a rubber bung. This tube should reach almost the bottom of the flask.

• Through the other hole of the rubber bung, a delivery tube is inserted which connects the flask and the condenser.
• The condenser is connected to a receiver flask using an adaptor. Provisions are made to heat the steam can and flask.

Steam Distillation Procedure:

The non-aqueous liquid is placed in the flask. A small quantity of water is added to it. Steam can is filled with water. The steam generator and the flask are heated simultaneously so that a uniform flow of steam passes through the boiling mixture.

• The mixture gets heated.
• The steam carries the volatile oil and passes into the condenser, which is cooled by cold water.
• The condensed immiscible liquid is collected into the receiver.
• Distillation is continued until all the non-aqueous liquid has been distilled. In the receiver, water and organic liquid form two separate layers, which can be easily separated using a separating flask.
• For volatile substances, which are miscible with water, distillation with steam would involve the same principle of fractional distillation.

Steam Distillation Applications:

• Steam distillation is used for the separation of immiscible liquids.
• This method is used for extracting most of the volatile oils such as clove, anise and eucalyptus.
• It is useful in the purification of liquid with high boiling point.
• Camphor is distilled by this method.
• Aromatic waters are prepared by this method.

Steam Distillation Advantages:

• Volatile oils can be separated at a lower temperature in steam distillation, without any decomposition and loss of aroma.
• If a substance has low volatility, it can be satisfactorily distilled, provided its molecular weight is considerably higher than water.

Steam Distillation Disadvantage:

Steam distillation is not suitable when immiscible liquid and water react with each other.

6. Molecular Distillation

Molecular distillation is defined as the process in which each molecule in the vapour phase travels the mean free path and gets condensed individually without intermolecular collisions on the application of a vacuum.

Molecular Distillation Principle:

The mean free path is the average distance travelled by the molecule in a straight line without any collision. The mean free path is inversely proportional to number of molecules to 1 cc of the gaseous phase.

• That means the mean free path can be increased by reducing the number of molecules per cc.
• The process is carried out at a pressure as low as 1 μhg.
• The number of molecules is drastically reduced and if a molecule is being heated under such conditions or pressure, the molecule escapes from the evaporating surface and travels a few cm without colliding with residual gas in the space above.

If a condensing surface is placed within this distance a major fraction of the molecule is condensed and will not return back to the distillant. Residual gas offers negligible resistance to the evaporation.

• The energy supplied for distillation is solely utilized to evaporate the compound and no energy is dissipated in the collisions.
• Therefore for a given temperature molecular distillation takes place at a very high rate or for a given distillation rate molecular distillation operates at a quite low temperature because the distillation travelled by the molecules is very short.
• It is also called short-path distillation.
• The distillate molecules should get a chance to reach the evaporating surface and therefore the layer of the distillate should be thin to overcome the pressure of the layer above to come to the surface (hydrostatic head).
• Therefore the distillant is maintained in a thin layer i.e., turbulent to provide best chance to the molecules to reach the surface.
• Vapour is evolved from the surface only and therefore is also called as evaporative distillation.

Molecular Distillation Applications:

• Purification of chemicals such as tricresyl phosphate, dibutyl phthalate and dimethyl phthalate.
• More frequently used in the refining of fixed oils.
• Vitamin A is separated from fish liver oil. Vitamin E is concentrated by this from fish liver oils and other vegetable oils.
• Free fatty acids are distilled at 100°C. Steroids can be obtained between 100 ’C and 200”C, while triglycerides can be obtained from 200 °C onwards.
• Proteins and gums Will remain as nonvolatile residues. Thus, the above molecular distillation.

7. Falling Film Molecular Still or Wiped Film Molecular Still

Falling Film Molecular Stil Principle:

In this method, vaporisation occurs from a film of liquid flowing down a heated surface under a high vacuum. The vapour (molecules) travels a short distance and strikes the condenser nearby. Each molecule is condensed individually. The distillate is subsequently collected.

Falling Film Molecular Stil Construction:

This consists of a vessel. This vessel has a diameter of one meter. The walls of the vessel are provided with suitable means of heating (jacket). Wipers are provided adjacent to the vessel wall.  Wipers are connected to a rotating head through a rotor.

The condensers are arranged very close to the wall (evaporating surface).  The vacuum pump is connected to a large diameter pipe at the centre of the vessel. Provisions are made for collecting the distillate and the undistilled liquid residue at the bottom.

Falling Film Molecular Stil Working:

The vessel is heated by suitable means. Vacuum is applied at the centre of the vessel and wipers are allowed to rotate. The feed is entered through the inlet of the vessel.  As the liquid flows down the walls, it is spread to form a film by PTFE (polytetrafluoroethylene) wipers, which are moving at a rate of 3 metres per second.

The velocity of the film is 1.5 metres per second. Since the surface is already heated, the liquid film evaporates directly. The vapour (molecules) travels its mean free path and strikes the condenser.  The condensate is collected into a vessel. The residue (undistilled or mean free path not travelled) is collected from the bottom of the vessel and re-circulated through the feed port for further distillation. Capacity is about 1000 litres per hour.

8. Centrifugal Molecular Still

Centrifugal Molecular Still Principle:

In this method, liquid feed is introduced into a vessel, which is rotated at a very high speed (centrifugal action). On account of heating, vapourisation occurs from a film of liquid on the sides of the vessel. The vapour (molecules) travels a short distance and gets condensed on the adjacent condenser. Each molecule is condensed individually. The distillate is subsequently collected.

Centrifugal Molecular Still Construction:

It consists of a bucket-shaped vessel having a diameter of about 1 to 1.5 metres. It is rotated at high speed using 2 motors. Radiant heaters are provided externally to heat the fluid in the bucket. Condensers are arranged very close to the evaporating surface. The vacuum pump is connected to the entire vessel at the top. Provisions are made for introducing the feed into the centre of the bucket, for receiving the product and residue for re-circulation.

Centrifugal Molecular Still Working:

Vacuum is applied at the centre of the vessel. The bucket-shaped vessel is allowed to rotate at high speed. The feed is introduced from the centre of the vessel. Due to the centrifugal action of the rotating bucket, the liquid moves outward over the surface of the vessel and forms a film.

Since the radiant heaters heat the surface, the liquid evaporates directly from the film. The vapour (molecules) travels its mean free path and strikes the condenser. The condensate is collected into another vessel. The residue is collected from the bottom of the vessel and is recirculated through the feed port for further distillation.

Distillation Pharmaceutical Engineering Multiple Choice Questions

Question 1. Water for injection is prepared by using

1. Simple distillation
2. Fractional distillation
3. Molecular distillation
4. Steam distillation

Answer: 1. Simple distillation

Question 2. Which one of the methods is also called differential distillation?

1. Simple distillation
2. Molecular distillation
3. Fractional distillation
4. Steam distillation

Answer:  1. Simple distillation

Question 3. Which one of the following methods is used for distillation of camphor?

1. Fractional distillation
2. Steam distillation
3. Simple distillation
4. Molecular distillation

Answer:  4. Molecular distillation

Question 4. Which type of liquid evaporates first in the distillation process?

1. Immiscible liquid
2. Non-volatile liquid
3. Less volatile liquid
4. More volatile liquid

Answer: 4. More volatile liquid

Question 5. Which method we can use for the preparation of the aromatic spirit of ammonia?

1. Simple distillation
2. Molecular distillation
3. Fractional distillation
4. Steam distillation

Answer: 1. Simple distillation

Question 6. Which type of distillation is called as evaporative distillation?

1. Simple distillation
2. Fractional distillation
3. Molecular distillation
4. Steam distillation

Answer: 3. Molecular distillation

Question 7. Why condenser is placed in an inclined position?

1. Collect the condensate easily
2. Remove the film of condensed liquid
3. To use the gravity principle effectively
4. Fast condensation

Answer: 3. To use the gravity principle effectively

Question 8. Separation of liquid by distillation is based upon one of the following?

1. Boiling point
2. Miscibility
3. Viscosity
4. Vapour pressure

Answer: 3. Viscosity

Question 9. Mean free path is associated with

1. Simple distillation
2. Flash distillation
3. Molecular distillation
4. Steam distillation

Answer: 4. Steam distillation

Question 10. Complete separation of individual components is not possible in

1. Simple distillation
2. Molecular distillation
3. Fractional distillation
4. Steam distillation

‘Answer: 2. Molecular distillation

Evaporation In Pharmaceutical Engineering Introduction

Evaporation is the process of a substance in a liquid state changing to a gaseous state due to an increase in temperature and or pressure.

Or

Evaporation is a process in which large quantities of liquid are vaporized to get a concentrated product by applying heat.

• Evaporation is a type of vapourization that occurs on the surface of a liquid as it changes into the gaseous phase.
• The surrounding gas must not be saturated with the evaporating substance.
• When the molecules of the liquid collide, they transfer energy to each other based on how they collide.
• When a molecule near the surface absorbs enough energy to overcome the vapour pressure, it will “escape” and enter the surrounding air as a gas.
• When evaporation occurs, the energy removed from the vaporized liquid will reduce the temperature of the liquid, resulting in evaporative cooling.
• Either suspension or solutions can be subjected to evaporation.
• The only condition is that the liquid must be volatile and the solute must be nonvolatile. Since heat is supplied the constituents must be thermo-stable.

Evaporation In Pharmaceutical Engineering Objectives

• One of the primary objectives of this evaporation is to reduce the volume of the product by some significant amount without loss of nutrient components.
• To make transport and storage easier as evaporation decreases the weight and volume of the product.
• To remove large amounts of liquid from the product before the dehydration process.
• To improve the stability of the product.

Evaporation Applications In Pharmaceutical Engineering

• Manufacture of bulk drugs: The evaporation process is used in the manufacture of bulk drugs in pharmaceutical industries.
• It is also used in the formulation of biological products like enzymes, antibiotics, vitamins etc.
• In demineralization of water.
• Film deposition: Thin films may be deposited by evaporating a condensing it onto a substrate, or by dissolving the substance in a so vent, spreading the resulting solution thinly over a substrate and evaporating the solvent,
• Industrial applications include many printing and coating processes, recovering s<a\U from solutions.
• Concentration of blood plasma and serum.
• Removal of water and solvent from fermentation broths.
• Concentration of herbal extract.

Factors Influencing The Rate Of Evaporation In Pharmaceutical Engineering

1. Temperature:

• Temperature is directly proportional to the rate of evaporation. Increase in temperature increases the rate of evaporation.
• At a given temperature some molecules possess more kinetic energy than the other molecules. Fast-moving molecules will move from the surface to the vapour state.
• While the molecules having less kinetic energy will remain in the bulk of the liquid.
• If the temperature is increased the molecules will get more energy and they will escape from the surface of the liquid.

2. Vapour pressure:

• The rate is directly proportional to the vapour pressure of the liquid. If the vapour pressure of the liquid is more then the rate of evaporation will be more.
• The lower the external pressure the lower the boiling point of liquid and hence greater will be the evaporation.
• This condition is achieved by using a vacuum. Saturation of the overhead space with vapours of liquid decreases the evaporation rate.
• If the air already has a high concentration of the substance evaporating, then the given substance will evaporate more slowly.

3. Flow rate of air:

• This is in part related to the concentration points above.
• If “fresh” air (i.e., air which is neither already saturated with the substance nor with other substances) is moving over the substance all the time, then the concentration of the substance in the air is less likely to go up with time, thus encouraging faster evaporation.
• This is the result of the boundary layer at the evaporation surface decreasing with flow velocity, decreasing the diffusion distance in the stagnant layer.

5. Inter-molecular forces:

• The stronger the forces keeping the molecules together in the liquid state, the more energy one must get to escape.
• This is characterized by the enthalpy of vapourization.
• So stronger intermolecular forces will require high energy to evaporate the molecules. So the rate of evaporation will get decreased

6. Surface area:

A substance that has a larger surface area will evaporate faster, as there are molecules per unit of volume that are potentially able to escape. are more surface

7. Type of product required:

• The type of product which has to be evaporated decides the method of evaporation equipment for evaporation.
• This affects not only the rate of evaporation but also the quality of the final product, For example, an Open pan produces liquid or dry concentrate, which.
• The vacuum as well as the evaporator give the porous product.

8. Film and deposits:

• Some products during concentration form a film on the surface of the liquid.
• This film formed reduces the evaporating surface and precipitated matter (on the surface) hinders the transfer of heat.
• This can be avoided by stirring.

Differences Between Evaporation And Other Heat Processes In Pharmaceutical Engineering

1. Difference between Evaporation and Distillation: 

2. Difference between Evaporation and Sublimation:

3. Difference between Evaporation and Boiling:

4. Difference between Evaporation and Drying

5. Difference between Evaporation and Crystallization:

Equipment Used For Evaporation In Pharmaceutical Engineering

The equipment used for evaporation is called as evaporator.

They are classified as follows:

1. Evaporator with the heating medium in the jacket

Example:  Evaporating pan

2. Vapour-heated evaporators with tubular heating surfaces

1. Evaporators with tubes placed horizontally

Example: Horizontal tube evaporator

2. Evaporators with tubes placed vertically

1. Evaporators with short tubes
   1. Single effect evaporators
      • Example:  Short tube vertical evaporator
   2. Multiple effect evaporator
      • Example:  Triple effect evaporator
2. Evaporators with long tubes
   1. Evaporators with natural circulation
      • Example:  Climbing film evaporator (Rising film evaporator}
   2. Evaporators with forced circulation
      • Example:  Forced circulation evaporator

Steam Jacketed Kettle (Evaporating Pan) In Pharmaceutical Engineering

Evaporating pans or steam-jacketed kettles come under the classification of natural circulation evaporators.

It. consists of a hemispherical pan surrounded by a steam jacket. The hemispherical shape provides a large surface area for evaporation. The evaporation pan may be fixed and the emptying of the pan can be done from the product outlet.

 Steam-jacketed kettles Principle:

The conduction and convection mechanism is involved in the evaporation process. So that the heat is transferred by this mechanism to the material placed for evaporation in the pan. Steam provides heat to the pan in which the material is placed. The temperature rises and the escaping tendency of the solvent molecules into the vapour increases and enhances the vapourization of the solvent molecules.

 Steam-jacketed kettles Construction:

The construction of the steam-jacketed kettle or evaporating pan consists of two hemispherical pans one is the kettle (inner pan) and the other is called the jacket (outer).

• These two pans are joined to each other enclosing a space through which steam is passed. Several metals are used as materials for the construction of the kettle.
• Copper is an excellent material but it gets dissolved in acidic liquids to solve this problem tinned copper is used. Iron is used for the construction of the jacket because it has minimum conductivity.
• At the top of the jacket inlet for steam is provided.
• The jacket has two outlets one is for uncondensed gases (on the opposite side of the inlet) and another is to remove condensate (at the bottom of the jacket).
• The kettle is provided with one outlet for the product discharge at its bottom.

 Steam-jacketed kettles Working:

The liquid to be evaporated is poured into a kettle. Steam is provided from the steam inlet of the jacket.  This steam increases the temperature of the liquid. The condensed steam is removed from the outlet at the bottom of the jacket. The continuous stirring is essential.

To remove vapour to prevent condensation of liquid litres and also to accelerate the rate of evaporation fans are fitted.  A kettle of capacity up to about 90 litres may be made to tilt. The concentrated product is collected from the outlet of the kettle at the bottom.

 Steam-jacketed kettles Uses:

• An evaporating pan or steam-jacketed kettle is suitable for concentrating aqueous liquids.
• An evaporating pan or steam-jacketed kettle is suitable for concentrating thermo-stable liquors such as liquorice extracts.

 Steam-jacketed kettles Advantages:

• Evaporating pan or steam-jacketed kettle is constructed both for small scale and large scale batch operations.
• Evaporating pan or steam-jacketed kettle is simple in construction and easy to operate, clean and maintain.
• Its cost of installation and maintenance is low.
• For the construction of the evaporating pan. materials such as copper, stainless steel aluminium and so on a wide variety of materials can be used.
• Stirring of the contents or materials and removal of the products is easy.

 Steam-jacketed kettles Disadvantages:

• Decomposition of the product occurs which gets deposited at the bottom.
• The heating surface is limited and decreases proportionally to increase in the size of the pan.
• It is not suitable for the concentration of thermo-labile materials because the liquid is heated throughout in an open atmosphere. Further, there is evaporate under a reduced pressure
• The evaporating pan cannot be used
• For the evaporation of thermo-labelile pharmaceutical materials which are dissolved in an organic solvent, such as ethyl alcohol, as there is no provision to recollect the costly organic solvents.

Horizontal Tube Evaporator In Pharmaceutical Engineering

Horizontal Tube Evaporator Principle:

In this type of evaporator, the steam is passed through the horizontal tubes. These tubes are immersed in a liquid to be evaporated. Heat transfer takes place through the tubes and the liquid outside the tubes gets heated. These heated tubes provide heat to the liquid. The Iquid gets evaporated. The concentrated liquid is collected from the bottom.

Horizontal Tube Evaporator Construction:

It consists of a cylindrical body. The lower body ring is provided with a steam compartment closed on the outside with cover plates and inside by tube sheets. Between the tube sheets, several horizontal tubes is fastened. There are outlets for non-condensed gases and condensed steam. Feed enters at a convenient point and thick liquor is collected at the bottom.

The evaporator is usually made of cast iron. The average size of the body is 6 to 8 ft. in diameter- and 8 to 12 ft in height. The tube tank is shallower and its width is around half the diameter of the body.

The liquor level is carried slightly above the tubes. The babes are attached in a typical manner. A thick tube sheet is used, holes are bored a little larger in diameter than the diameter of the tubes and conical rubber gaskets are slipped into the tubes;o that tubes fit into the tube sheet.

Each set of 4 tubes is secured by drawing down a packing pate-held in place by a nut. Such an arrangement facilitates the removal of tubes. Tubes are long enough to project about 1/2″ beyond the tube sheet at either end

Horizontal Tube Evaporator Working:

Feed is introduced into the evaporator until the tubes are immersed. Steam is introduced into the steam compartment. Tubes receive heat from steam and conduct it to liquid. Steam condensate passes through the corresponding outlet. Feed receives heat and solvent gets evaporated. Vapour escapes through the outlet placed on the top. This process is continued until a thick liquid is formed which is collected from the outlet at the bottom.

Horizontal Tube Evaporator Use:

It is used for non-viscous solutions that do not deposit crystals on evaporation.

Horizontal Tube Evaporator Advantages:

• The cost of per square meter of heating surface is less in horizontal tube evaporator.
• It provides a more heating surface for evaporation.
• It requires less space for installation.
• It is cheap.

Horizontal Tube Evaporator Disadvantages:

• Liquid circulation is poor in this evaporator.
• The formation of a semisolid layer on the evaporating surface reduces heat transfer rates.
• Not suitable for viscous liquids.

Climbing Film Evaporator In Pharmaceutical Engineering

In a typical climbing film evaporator, the heat exchanger is mounted vertically and the evaporator liquid flows in an upward direction through the tubes. Water in the ev<iporator liquid boils as the liquid rises in the tubes. This boiling action helps force liquid up and out of the tubes. The liquid and vapour leave the heat exchanger together and enter the vapour body. After vapour separation, the evaporator liquid flows from the vapour body through the circulating pump to the heat exchanger.

Climbing film evaporator Principle:

In this evaporator, tubes are heated externally using steam. The liquid is to be evaporated is heated before entering these tubes. The liquid is then allowed to flow through these heated tubes. The liquid near the walls of heated tubes starts to evaporate by forming bubbles. These bubbles fuse and form larger bubbles, which travel up in the tubes. The liquid films are blown up from the top of the tubes and the strike entrainment separator (deflector) is kept above. This throws the liquid concentrate down into the lower part from where it is withdrawn.

Climbing film evaporator Construction:

In this evaporator, the heating unit consists of steam-jacketed tubes. Here, the tubes are held between two plates. An entrainment separator is placed at the top of the vapour head. The evaporator carries a steam inlet, vent outlet and condensate outlet. The feed inlet is from the bottom of the steam compartment

Climbing film evaporator Working:

The preheated liquid feed is entered from the bottom of the evaporator. Steam into the spaces around the tubes through the inlet. The temperature of the liquid increases due to the heated walls of the tubes. The liquid starts to evaporate as its temperature go on increasing.

The evaporated part of the liquid forms small bubbles. These bubbles unite to form bubbles of size equal to the size of the width of the tubes. These bubbles trap a part of the liquid (slug) when going upward through the tubes. As more vapour is formed, the slug of liquid is blown up in the tubes facilitating the liquid to spread as a film over the walls.

This film of liquid continues to vaporize rapidly. Finally, the mixture of liquid concentrate and vapour is ejected at a high velocity from the top of the tubes. The entrainment separator prevents entrainment as well as it breaks the foam. The vapour leaves from the top, while the concentrate is collected from the bottom.

Climbing film evaporator Uses:

• Using climbing film evaporator, thermo labile substances such as insulin, liver extracts and vitamins can be concentrated.
• Clear liquids, foaming liquids and corrosive solutions in large quantities can be operated.
• Deposit of scales can be removed quickly by increasing the feed rate or reducing the steam rate so that the product is unsaturated for a short time.

Climbing film evaporator Advantages:

• Long and narrow tubes provide a large surface area.
• Very high film velocity reduces boundary layers to a minimum giving improved heat transfer.
• The contact time between the liquid and the heating surface is very short. So, it is suitable for heat-sensitive materials.
• Unlike short tube evaporators, the tubes not submerged. So there is no elevation of boiling point due to hydrostatic head.
• It is suitable for foam-forming liquids because foam can be broken by an are entrainment separator.

Climbing film evaporator Disadvantages:

• Climbing film evaporator is expensive.
• Construction is quite complicated.
• It is difficult to clean and maintain.
• It is not advisable for very viscous liquids.

Forced Circulation Evaporator In Pharmaceutical Engineering

 Forced Circulation Evaporator Principle

In a forced circulation evaporator, the liquid is circulated through the tubes at high pressure using a pump. Hence boiling does not take place because the boiling point is elevated. Forced circulation of the liquids also creates some form of agitation. When the liquid leaves the tubes and enters the vapour head, the pressure falls suddenly. This lead to the flashing of super-heated liquor. Thus evaporation is affected.

 Forced Circulation Evaporator Construction and Working:

Any evaporator that uses a pump to ensure higher circulation velocity is called a forced circulation evaporator. Forced circulation evaporators are used if boiling of the product on the heating surfaces is to be avoided due to the fouling characteristics of the product, or to avoid crystallization. The flow velocity in the tubes must be high, and high-capacity pumps are required.

The liquid is typically heated only a few degrees for each pass through the heat exchanger, which means the recirculation flow rate has to be high. This type of evaporator is also used in crystallizing applications because no evaporation, and therefore no concentration increase, takes place on the heat transfer surface.

Evaporation occurs as the liquid is flash-evaporated in the separator/flash vessel. In’ crystallizer applications this is then where the crystals form, and special separator designs are used to separate crystals from the recirculated crystal slurry. The heat exchanger (in evaporator parlance sometimes called the “calandria”) can be arranged either horizontally or vertically depending on the specific requirements in each case

 Forced Circulation Evaporator Uses:

• If evaporation is conducted under reduced pressure, a forced circulation evaporator is suitable for thermo-labile substances.
• This method is used for the concentration of insulin and liver extracts.
• It is well suited for crystallizing operations where crystals are to be suspended at all times.

 Forced Circulation Evaporator Advantages:

• In a forced circulation evaporator, there is rapid liquid movement due to a high heat transfer coefficient.
• Salting, scaling and fouling are not possible due to forced circulation.
• This evaporator is suitable for labile substances because of rapid evaporation.
• It is suitable for viscous preparation because a pumping mechanism is used.

 Forced Circulation Evaporator Disadvantages:

• In a forced circulation evaporator the hold-up of liquids is high.
• The equipment is expensive because the power is required for the circulation of the liquids.

Multiple Effect Evaporator In Pharmaceutical Engineering

In single effect evaporator steam is used to heat the liquid which provides the latent heat ‘ of vapourization. The vapours are condensed in the condenser where the latent is given up to the cooling water and goes to waste.

To avoid this wastage two evaporators are connected with the piping arrangement so that the vapour from the calandria of the first effect is used to heat the calandria of the second effect. This means that the calandria of the second effect is used as a condenser for the first time.

So that the latent heat of vapourization is used to evaporate more quantity of the liquid instead of its going to waste. The vapour from the second effect is then taken to a condenser and converted into liquids. In general, not more than two or three effects are combined to have economical and efficient evaporation of liquids

Different types of feed arrangement of multiple effect evaporators:

1. Forward feed arrangement:

In this arrangement, the feed and steam introduced in the first effect and pressure in the first effect is highest and pressure in the last effect is minimum, so transfer of feed from one effect to another can be done without a pump.

2. Backward feed arrangement:

In this arrangement, feed is introduced in the last effect and steam is introduced in the first effect. For the transfer of feed, it requires a pump since the flow is from low pressure to higher pressure. Concentrated liquid is obtained in the first effect.

3. Mixed feed arrangement:

In this arrangement, feed is introduced in intermediate effect, flows in forward feed to the end of the series and is then pumped back to the first effect for final concentration. This permits the final evaporation to be done at the highest temperature.

Multiple Effect Evaporation In Pharmaceutical Engineering

Multiple Effect Evaporation Principle:

When the evaporator is fed with steam it boils the water present as feed. The water vapour produced has a large amount of heat which will go to waste if it is condensed. Therefore, in such case, evaporator makes very poor use of steam. The vapour used is suitable for passing to the calendria of the second evaporator where it is used as a heating medium.

If an evaporator is fed with steam at 126°C and it is evaporating water at 100°C then the water vapours coming off will also be at the temperature of 100° C and if these vapours are being used as the heating medium, water inside should boil at a lower temperature to maintain the temperature gradient for heat transfer. For this purpose vacuum should be drawn in the second evaporator to reduce the boiling point of water.

Multiple Effect Evaporation Construction:

The construction uses 3 evaporators i.e. Triple effect evaporator. The other aspects of the construction of the vertical tube evaporator remain the same. Vapour from first evaporator serves as the heating medium for the second and that from the second serves as a heating medium for the third evaporator. The last evaporator is connected to a vacuum pump

Multiple Effect Evaporation Working:

In the beginning, the multiple-effect evaporator is at room temperature and atmospheric pressure.

Liquid feed is introduced in all the 3 evaporators and the following operations are performed:

• Vent valves v₁, v₂, v₃ are open and other valves are closed.
• A vacuum is created in liquid chambers.
• Steam valve si and condensate valve Di are opened. Steam is supplied. Steam’ initially replaces cold air in the steam space of the first evaporator. When air is removed valve V₁ is closed.
• Steam is supplied till pressure P0 steam is created in steam space so that the temperature of the steam is t₀.
• Steam gives its temperature to liquid feed in the first evaporator and gets condensed.
• Condensate is removed through valve D₁.
• Liquid temperature increases and reaches boiling point ti, and vapour is generated exerting pressure p₁.
• This vapour displaces air in the upper part of the first evaporator and the steam space of the second evaporator.
• After the air is completely displaced from the steam space of the second evaporator, valve v₂ is closed.
• Vapour transmits heat t₁ to liquid in the second evaporator and gets condensed.
• Condensate is removed through valve D₂. Similar steps are continued in 3rd evaporator.

The steam to the first evaporator is at temperature t0 and pressure po. Feed is initially at room temperature. Steam gives its heat to feed. The difference in temperature of steam and feed reduces, Therefore the rate of condensation reduces. Therefore pressure in the vapour space of the first evaporator gradually increases to Pi. Increasing temperature to ti at which liquid boils in the first evaporator. The temperature gradient now is t₀– t₁.

The vapour from the first evaporator is now at a temperature ti and cannot boil the liquid in.

• For the second evaporator if its boiling point remains t₁ there will be no temperature gradient.
• In such case vacuum is drawn in the first evaporator so that liquid boils at t₂ and t₂ < t₂ so that the temperature gradient: of t₁– t₂ is maintained.
• The vapour in the first evaporator exerts pressure at P₂. Similar is the case with the third evaporator.
• As toiling proceeds liquid level in the first evaporator goes down. Feed is introduced through.
• The eed valve to maintain the liquid level constant. Similarly, feed is supplied to second and third-effect evaporators through valves F₂ and F₃.
• When the liquid in all three 3 evaporators is sufficiently concentrated, product valves are opened to collect the thick liquid.
• There is a continuous supply of steam and feed and a continuous withdrawal of products. The evaporator works continuously.

Multiple Effect Evaporation Uses:

• Vertical tube evaporator or short tube evaporator is used in the manufacture of the cascara extract.
• Vertical tube evaporator or short tube evaporator is used in the manufacture of salts
  and caustic soda.

Multiple Effect Evaporation Advantages:

• It is suitable for large-scale and continuous operation.
• It is highly economical when compared with a single effect.
• About 5 evaporators can be attached.

Economy of multiple effect evaporator:

The economy of the evaporator is the quantity of vapour produced per unit of steam admitted. It is calculated by considering the following assumptions. Feed is admitted at its boiling point. Therefore it does not require more heat to raise its temperature. Hence, the supplied steam gets condensed to give heat of condensation. This heat is then transferred to the liquid. The heat transferred now serves as latent heat of vapourization, i.e. Liquid undergoes vapourization by receiving heat. Loss of heat by any means is negligible.

The economy of the evaporator may be expressed as:

⇒ Economy of evaporator = Total mass of vapour produced/ Total mass of stem supplied

In a single effect, the evaporator stem is produced only once. Hence

⇒ The economy of a single effect evaporator = N units of vapour produced / N units of stem supplied = 1

In a multiple-effect evaporator, one unit of steam produces vapour many times, depending on the number of evaporators connected. Hence,

⇒ The economy of a multiple effect evaporator = N units of vapour produced/ 1 unit of stem supplied Not

So, the economy of the multiple effect evaporators is equal to the number of units connected multiplied by the economy of the single evaporator

Evaporation In Pharmaceutical Engineering Multiple-Choice Questions

Question 1. Which operation is generally carried out after evaporation?

1. Distillation
2. Crystallization
3. Extraction
4. Drying

Answer: 4. Drying

Question 2. Which condition should liquid fulfil to undergo the evaporation process?

1. Liquid should be volatile
2. Liquid should be viscous
3. Solent should not be volatile
4. Constituents must be heat-sensitive

Answer: 1. Liquid should be volatile

Question 3. What is the purpose of the entrainment separator in the climbing film evaporator?

1. Allowing the heat to transfer
2. Breaking the foam
3. Allowing the vapour to escape
4. Pulling the liquid up

Answer: 2. Breaking the foam

Question 4. Calendario consist of the number of

1. Baffles
2. Tubular surface
3. Outlets
4. Jackets

Answer: 2. Tubular surface

Question 5. What is the problem one can face during evaporation in climbing film evaporators?

1. Film formation
2. Droplet formation
3. Entrainment of liquid
4. The boiling point of liquid

Answer: 3. Entrainment of liquid

Question 6. Which evaporator gives the porous final product after evaporation?

1. Vacuum evaporator
2. Multiple effect evaporators
3. Pan Evaporator
4. Climbing film evaporator

Answer: 4. Climbing film evaporator

Question 7. Evaporation is carried out in which one of the following conditions?

1. At the boiling temperature
2. Room temperature
3. Above the boiling temperature
4. Below the boiling temperature

Answer: 3. Above the boiling temperature

Question 8. Which one of the following factors does not affect the evaporator?

1. Melting point of solids
2. The boiling point of liquids
3. Viscosity of liquid
4. Surface area of the evaporator

Answer: 1. Melting point of solids

Question 9. A triple-effect evaporator uses the concept of one of the following evaporators?

1. Vertical tube evaporator
2. Pan evaporator
3. Climbing film evaporator
4. Vacuum evaporator

Answer: 1. Vertical tube evaporator

Question 10. Feed is preheated in one of the following evaporators?

1. Climbing film evaporator
2. Pan evaporator
3. Vacuum evaporator
4. Forced circulation evaporator

Answer:  1. Climbing film evaporator

Size Separation Introduction

Size separation is a unit operation that involves the separation of particles of a particular size range from a mixture of different-sized particles. It is generally the step next to the size reduction. After size reduction particles prepared have wide size distribution. The narrow size distribution is necessary to confer equal physicochemical properties. It is necessary for pharmaceutical preparations like suspensions to avoid Ostwald ripening in tablets to form granules.

Official Standards For Powder Size

According to Indian pharmacopeia, the size of the powder is expressed by a mesh the aperture size of the sieve through which powder can pass.

I.P. categorizes powders as follows:

•  Coarse powders: A powder of which all the particles pass through a sieve with a nominal mesh aperture of 1.70 mm (No. 10 sieve) and not more than 40% through a sieve with a nominal mesh aperture of 355 pm (No. 44 sieve) is called coarse powder.
• Moderately coarse powder: A powder of which all the particles pass through a sieve with a nominal mesh aperture of 710 pm (No. 22 sieve) and not more than 40% through a sieve with a nominal mesh aperture of 250 pm (No. 60 sieve) is called moderately coarse powder.
• Moderately fine powder: If all particles of powder pass through a sieve with a nominal aperture of 355 pm (No. 44 sieve) and not more than 40% through a sieve with a nominal mesh aperture of 180 pm (No. 85 sieve) is called the moderately fine powder.
• Fine powder: If all the particles pass through a sieve with a nominal mesh aperture of 180 pm (No. 85 sieve) it is called a fine powder.
• Very fine powder: If all the particles pass through a sieve with a nominal mesh aperture of 125 pm (No. 120 sieve), it is called a very fine powder. In the United States Pharmacopoeia, powders are classified according to size as very coarse, coarse, moderately fine, fine, and very fine.

d₅₀ is the smallest sieve opening through which 50% or more of the material passes

Objectives Of Size Reduction

• To obtain powders of desired size distribution. Any solid material after size reduction gives particles of different sizes. So to get the particles of the desired size range one must go through the size separation.
• During tablet granulation the granules should be within a narrow size range, otherwise, weight variation will take place during tablet punching.
• To obtain a stable suspension. If the dispersed phase contains particles of a wide size range then they may increase the Ostwald ripening.
• To avoid the variations in physicochemical properties.
•  To set a quality control parameter for raw material.
• To improve mixing.

Applications Of Size Reduction Size Separation In Pharmaceutical Engineering

• Capsule filling: Uniform size particles are easy to fill in the capsules giving good flow properties.
• Tablet formulation: Uniform particle size ensures good flow from the hopper which avoids weight variation.
• It can serve as a quality control tool for the evaluation of raw materials.
• Removal of impurities based on size.
• Separation of solids from a gas suspension.
• Separation of coarse particles after levigation.
• Drugs that are intended for oral use should have a very small size (10 pm). So, much smaller-sized particles are separated by centrifugal classifiers.
• In the extraction process, the optimum size is needed to use for efficient extraction. For example, for extraction from Ashoka bark coarse powder is specified whereas for extraction from Rauwolfia root a moderately coarse powder is indicated.

Size Separation Sieves Size Separation In Pharmaceutical Engineering

A sieve is a surface having several apertures of specific dimensions.

• A material to be sieved is passed on the surface of the screen and agitated.
• The particles having a size less than the aperture size of the sieve are passed through the sieve where whereas the particles having a size more than the aperture are retained on the surface of the sieve.
• So, the particles of material get separated based on their size after sieving. By using sieves of different sizes the powder can be separated and graded.
• Sieves for pharmacopoeial testing are constructed from wire cloth with square meshes, woven from wires of brass, bronze, stainless steel, or any other suitable metal
• The wires should be of uniform circular cross-section and should not be coated or plated. Sieve metals should be compatible with the drugs to be screened.

Standards for Sieves

Sieves used for pharmacopoeial testing must specify the following:

• Number of sieves: The sieve number indicates the number of meshes in a length of 2.54 cm in each transverse direction parallel to the wires.
• Nominal size of aperture: Nominal size of aperture indicates the distance between the wires. It represents the length of the side of the square aperture. The I.P. has given the nominal mesh aperture size for the majority of sieves in mm or in μm.
• Nominal diameter of the wire: Wire mesh sieves are made from the wire having the specified diameter to give suitable aperture size and sufficient strength to avoid distortion of the sieve.
• Approximate percentage sieving area: This standard expresses the area of the meshes as a percentage of the total area of the sieve. It depends on the size of the wire used for any particular sieve number. Generally, the sieving area is kept within the range of 35 to 40 percent to give suitable strength to the sieve.
• Tolerance average aperture size: Some variation in the aperture size is unavoidable and when this variation is expressed as a percentage, it is known as the ‘aperture tolerance average’.
  • It is a limit given by pharmacopeia within which a particular dimension or average aperture size can be allowed to vary and still be acceptable for the purpose for which it is used.
  • Fine meshes cannot be woven with the same accuracy as coarse meshes.
  • Hence the aperture tolerance average is smaller for coarse sieves than the fine sieves.

Size Separation Mechanisms

Mechanical sieving devices are usually based on methods that agitate or brush the sieve or use centrifugal force.

1. Agitation: Sieves may be agitated in several different ways, for example:
   • Oscillation: The sieve is mounted in a frame that oscillates back and forth. The method is simple. The material may roll on the surface of the sieve, fibrous materials can form a ball of material.
   • Vibration: In this method, the sieve is vibrated at high speed electrically. The high speed of vibration is applied to the particles on the sieve. So the particles do not block the mesh.
   • Gyration: The gyratory method uses a system in which the sieve is on a rubber mounting and connected to an eccentric flywheel.
     • Thus, the sieve is given a rotary movement of small amplitude, but of considerable intensity, giving a spinning motion to the particles.
     • This increases the chances of a particle becoming suitably oriented to pass through the mesh so that the output is usually considered greater than that obtained with oscillating or vibratory sieves.
     • Agitation methods may be made continuous, by the inclination of the sieve and the provision of separate outlets for undersized and oversized particles.
     • This applies irrespective of the method of agitation.
2. Brushing: A brush can be used to move the particles on the surface of the sieve and to keep the meshes clear. A single brush across the diameter of an ordinary circular sieve, rotating about the mid-point is effective, but in large-scale production, a horizontal cylindrical sieve is employed, with a spiral brush rotating on the longitudinal axis of the sieve.
3. Centrifugal: A mechanical sieve of this type normally uses a vertical cylindrical sieve with a high-speed rotor inside the cylinder, so that particles are thrown outwards by centrifugal force. The current of air created by the movement assists sieving also, and is especially useful with very fine powders

Size Separation Instruments Size Separation In Pharmaceutical Engineering

1. Sieve Shaker

Sieve Shaker Principle:

The materials are separated based on their size due to high-speed vibratory motion. The finest particles are collected at the bottom sieve or the collecting pan and the particles having the largest size are collected in the upper sieve.

Sieve Shaker Construction:

In the sieve shaker, a set of sieves is used. These sieves are arranged in descending order i.e. sieve of a larger size is at the top and the sieve having the smallest size is placed at the bottom. The bottom sieve is attached to the receiving pan. The size separation is done by passing the powder through these sieves.

Sieve Shaker Working:

The powder is placed in the upper sieve. The sieves are shaken with the help of mechanical sieve shakers or electromagnetic devices. This motion helps the particles to pass through the sieve. After a particular period of shaking some weight of the powder is retained on each sieve depending on its size

Sieve Shaker Use:

It can be used for handling a variety of dry powders, granules, and dry foods.

Sieve Shaker Advantages:

• It requires less area for operation.
•  It is a fast and more accurate process.
• High speed of vibration avoids the blockage of the sieve.

Sieve Shaker Disadvantage:

Sieves should be used and stored with care, since if the sieve becomes damaged or distorted then it is of little value.

2. Cyclone Separator

Very low rates of separation are achieved if separation is done under the influence of gravitational force, especially at low velocities and low particle size. So, the separation can be enhanced by using centrifugal force. The cyclone separator works based on centrifugal force.

Cyclone Separator Principle:

In a cyclone separator, centrifugal force is used to separate solids from fluids. The separation process depends on particle size and particle density. It is also possible to allow fine- particles to be carried with the fluid.

Cyclone Separator Construction:

It consists of a short vertical, cylindrical vessel with a conical base. The upper part of the vessel is fitted with a tangential inlet The solid outlet is at the base. A fluid outlet is provided at the center of the top portion, which extends inwardly into the separator. Such an arrangement prevents the air from short-circuiting directly from the inlet to the outlet of the fluids.

Cyclone Separator Working:

The solids to be separated are suspended in a stream of fluid (usually air or water). Such feed is introduced tangentially at a very high velocity so that rotary movement takes place within the vessel. The centrifugal force throws the particles to the wall of the vessel. As the speed of the fluid (air) diminishes, the particles fall to the base and are collected at the solid outlet. The fluid (air) can escape from the central outlet at the top.

Cyclone Separator Advantages:

• Low capital cost.
• Relative simplicity and few maintenance problems.
• Low-pressure drop (ca. 2-6 w.c.).
• Dry collection and disposal.
• Relatively small space requirements.
• No moving parts.
• Can be used under extreme processing conditions.

Cyclone Separator Disadvantages:

• Offer low particulate collection efficiencies, especially for particulate sizes below 5 pm.
• Inability to handle sticky materials.

Cyclone Separator Uses:

• Cyclone separators are used to separate solid particles from gases.
• It is also used for size separation of solids in liquids.
• It is used to separate the heavy and coarse fractions from fine dust.
• It is used in oil refineries to separate oils and gases.

3. Air Separator

Air Separator Principle:

The cyclone separator alone cannot- carry out size separation on fine materials. For such separations, a current of air combined with centrifugal force is used. The finer particles are carried away by air and the coarse particles are thrown by centrifugal force, which fall at the bottom.

Air Separator Construction:

It consists of a cylindrical vessel with a conical base. A rotating plate is fitted on a shaft placed at the center of the vessel. A set of fan blades are also fitted with the same shaft.

At the base of the vessel, two outlets are provided:

1. One for the finer particles and
2. The other is for coarse particles.

Air Separator Working:

The disc and the fan are rotated using a motor. The feed (powder) enters at the center of the vessel and falls on the rotating plate. The rotating fan blades produce a draft (flow) of air in the direction. The fine particles are picked up by the draft of air and carried into the space of the settling chamber, where the air velocity is sufficiently reduced so that the fine particles are dropped and removed through the fine particle outlet. Particles too heavy to be picked up by the air stream are removed at the coarse particle outlet

Air Separator Uses:

Air separators are often attached to the ball mill or hammer mill to separate and return oversized particles for further size reduction

Air Separator Advantages

• It gives efficient separation in smaller apparatus.
• The waste does not interact with the generator of the airflow, avoiding wear and clogging.
• Low maintenance.
• High reliability.
• Low-pressure drop.

Air Separator Disadvantages

• Low separation yield.
• Unsuitable for separating smaller particles.

4. Filter Bag

Filter Bag Principle:

In filter bags, the separation of fine powder from coarse powder is carried out by applying suction. Firstly the mixture of powder which is to be separated is passed through a bag which is made up of cloth by applying suction at opposite side of the feeding. This causes the separation of fine and coarse powder. After this separation, the bags are shaken by giving pressure to remove the powder that is adhered to the bags. After that powder is collected from a conical base.

Filter Bag Construction:

It consists of several bags made of cotton or wool fabric. These are suspended in a metal container. A hopper is arranged at the bottom of the filter to receive the feed. At the top of the metal container, a provision is made for a vacuum fan and exhaust through the discharge manifold. At the top of the vessel, a bell-crank lever arrangement is made to change the action from filtering to shaking

Filter Bag Working: 

• Filtering period: During this period the vacuum fan produces a pressure lower than the atmospheric pressure within the vessel. Gas to be filtered enters the hopper, passes through the bags, and out of the top of the apparatus. The particles are retained within the bags.
• Shaking period: During this period the bell-crank lever first closes the discharge manifold and air enters through the top so the vacuum is broken. At the same time, it gives a violent jerking action to the bags so that they are freed from the dust. The fine particles are collected at the conical base.

Filter Bag Uses:

• Bag filters are used along with other size separation equipment, e.g. a cyclone separator.
• They are used on the top of a fluidized bed dryer for drying to separate the dust.
• They are used to clean the air of a room.
• The household vacuum cleaner is a simple version of a bag filter.

Filter Bag Advantages: 

• A bag filter is extremely useful for removing fines, which cannot be separated by other methods.
• These can be used to remove dust.
• Reduced sensitivity to particle size distribution.
• No high voltage requirements

Filter Bag Disadvantages:

• It has a high resistance which is about 600-1200 P.
• Fabric life may be substantially shortened in the presence of high-acid or alkaline atmospheres, especially at elevated temperatures.
• Collection of hygroscopic materials or condensation of moisture can lead to fabric plugging, loss of cleaning efficiency, and large pressure losses.

5. Elutriation Tank

Elutriation is a method of separation of particles based on their density. The smaller size particles have low density whereas the particles of larger size have more density. These particles are separated using a fluid flow.

Elutriation Tank Principle:

The separation in the elutriation tank is based on the density of the particles which depends on the size of the particles. After levigation, the material is kept in an elutriating tank and mixed with a large quantity of water. Then depending on the density of the particle it will either settle down or it will be suspended in water. Then the sample is collected at different heights.

Elutriation Tank Construction:

The apparatus consists of a vertical column with an inlet near the bottom of the suspension, an outlet at the base for coarse particles, and an overflow near the top of fluid and fine particles. One column will give a single separation into two fractions. If more than one step separation is required multiple tubes can be used in a serial connection.

Elutriation Tank Working:

The material which is to be separated is first legated. Then this paste or powder is kept in an elutriating tank and a large quantity of water is poured into the tank. The content of the tank is mixed with the water by stirring. The particles are uniformly distributed in the water. They are allowed to settle for some time.

The particles which are having large sizes (high density) will settle down and the particles with smaller sizes will remain suspended in the liquid. If the tank contains outlets at different heights then the multiple fractions can be separated by containing the particles of different size ranges. Then these fractions are dried to collect the powder.

Elutriation Tank Uses:

This technique is useful for separation of insoluble solids. These solids are first subjected to grinding and then elutriation.

Elutriation Tank Advantages:

• It is a continuous process.
• Several fractions can be collected by using columns of different areas.
• The separation is quick as compared to sedimentation.

Elutriation Tank Disadvantage:

Dilution of suspension may be undesirable in some cases

Size Separation Size Separation In Pharmaceutical Engineering Multiple Choice Questions

Question 1. Which one of the following indicates a nominal size of aperture?

1. Area of mesh as a percentage
2. Distance between two adjacent wires
3. Number of meshes per linear length
4. A wire having a specified diameter that gives a suitable aperture

Answer:  3. Number of meshes per linear length

Question 2. Size classification is also known as

1. Size separation
2. Size reduction
3. Size distribution
4. Size analysis

Answer: 1. Size Separation

Question 3. The brushing method enhances the movement of

1. Coarse materials
2. Light materials
3. Sticky materials
4. Crystalline materials

Answer:  3. Sticky materials

Question 4. In cyclone separator, the separation depends on

1. Density and shape
2. Shape and surface area
3. Size and density
4. Surface texture and size

Answer: 3. Size and density

Question 5. In the air separator centrifugal force for the circulation of air is supplied by

1. Applying vacuum
2. Atomizing air
3. Pumping
4. Rotating blades

Answer: 4. Rotating blades

Question 6. Which mechanism helps in size separation by the sieve shaker?

1. Centrifugal force
2. Sedimentation
3. Brushing
4. Shearing forces

Answer: 4. Shearing forces

Question 7. A screen that sharply separates the feed mixture is called as

1. Actual screen
2. Ideal screen
3. Virtual screen
4. Real screen

Answer: 4. Real screen

Question 8. The disadvantage of a sieve shaker is

1. Attrition
2. Capacity limited
3. Expensive equipment
4. Tedious

Answer: 2. Capacity limited

Question 9. The movement of particles can be enhanced during size separation by one of the following modes.

1. Agitation
2. Attrition
3. Gravitation
4. Mixing

Answer: 1. Agitation

Size Reduction In Pharmaceutical Engineering Introduction

The raw materials are generally present in large size which cannot be used by industries so, so materials need to be converted into smaller-sized particles or powder. Conversion of large-sized material into small-sized particles or powder is called as size reduction.

This process is extensively used in pharmaceutical industries.

• Any lumpy amorphous or crystalline substance that is to be subsequently processed, whether organic or inorganic, vegetable or animal origin must undergo thorough size reduction.
• Size reduction increases the surface area of the material which enhances many properties of the drugs like dissolution, drying, extraction of the active constituents from crude drugs, etc.
• Size reduction is an important process involving crushing, cutting, pulverization, shredding etc.
• The action of reducing a material, especially a mineral ore, to minute particles or fragments is called as comminution.

Size Reduction In Pharmaceutical Engineering Objectives

Size reduction increases surface area.

1. An increase in surface area enhances the speed of many processes like chemical reactions, extraction of drugs, drying, dissolution rate, and rate of absorption.
2. Size reduction produces particles in a narrow size range. Mixing powders with a narrow size range is easier.
3. In the case of suspensions, fine particle size is important because it reduces the rate of sedimentation.
4. Pharmaceutical capsules, insufflations (i.e. powders inhaled directly into the lungs), suppositories, and ointments require smaller particle sizes.
5. To allow the rapid penetration of solvent in crude drugs to extract phytochemicals.

Size Reduction Mechanism In Pharmaceutical Engineering

Size reduction involves the following mechanisms:

1. Cutting
2. Compression
3. Impact
4. Attrition
5. Combination of impact and attrition

1. Cutting:

In this method of size reduction, the material is cut down into small pieces with the help of a sharp blade, knife, etc. It involves the application of force over a very narrow area of material using the sharp edge of the cutter. In industries, cutter mills are used to reduce the size of materials. This method gives generally a coarse-sized powder. This method can be used for size reduction of soft materials like roots, peels, etc.

2. Compression:

In this mechanism, the size reduction is achieved by crushing the material by application of pressure. Roller mill is used in industry to reduce the size involving the principle of compression.

3. Impact:

Impact occurs when the material is kept stationary and is hit by an object moving at high speed or when the material is kept moving at high speed against a stationary object. The hammer mill works on the principle of impact.

4. Attrition:

It involves a collision between two particles having high kinetic energy or a high-velocity particle with a stationary phase. A roller mill works on this principle.

5. Combined impact and attrition:

This type of mechanism involves both effects i.e. impact and attrition. A ball mill works on the combined principle of impact and attrition.

Size Reduction Laws Governing

They are used to predict energy requirements for size reduction.

1. Rittinger’s law
2. Kick’s law
3. Bond’s law
4. Holmes law
5. Harris law

1. Rittinger’s law:

The energy required in crushing is proportional to the new surface created as a result of particle fragmentation.

i.e. Energy ∝  New surface

Energy = [K1/D₂-1/D₁]

Where Di and D2 are particle sizes at the start and end of the process respectively.

⇒ K= K_R.F_C

Where K_R is Rittinger’s constant and fc is the crushing strength of the material.

2. Kick’s low:

The energy required to reduce the size of particle Is proportional to the ratio of the Initial size of the particle to the final size of the particle.

E = K_K In [d₁/d₂]

E = Energy required

K_K = Kick’s constant

D₁ = Average initial size of particles

D₂ = Final particle size (in logarithm).

3. Bond’s law:

The total work input required to reduce particle size is proportional to the square root of the diameter of the product particles.

W = 10 W_i1/√d₂-1/√d₁

Where,

W is the energy consumed,

D_υ is the size of the feed

D2 is the size of the product

W_i is the bond index.

Size Reduction Factors Affecting

1. Hardness:

The hardness of the material affects the process of size reduction. It is easier to break soft material to a small size than hard material.

2. Toughness:

The crude drugs of a fibrous nature or those having higher moisture content, are generally tough. A soft but tough material may present more problems in size reduction, than a hard but brittle substance.

3. Stickiness:

Stickiness causes a lot of difficulty in size reduction. This is because the material adheres to the grinding surfaces or sieve surface of the mill. It is difficult to powder drugs of have a gummy or resinous nature if the method used for size reduction generates heat. Complete dryness of the material may help to overcome this difficulty.

4. Material structure:

Materials that show some special structure may cause problems during size reduction e.g. vegetable drugs which have cellular structure, generally produce long fibrous particles on its size reduction. Similarly, a mineral substance having lines of weakness, produces flake-like particles on its size reduction.

5. Moisture content:

The presence of moisture in the material influences a number of its properties such as hardness, toughness, or stickyness which in its turn affects the particle size reduction. The material should be either dry or wet. It should not be damp. The material having 5% moisture in the case of dry grinding and 50% moisture in wet grinding does not create any problems.

6. Softening temperature:

Waxy substances such as stearic acid or drugs containing oils or fats, become softened during the size reduction processes if heat is generated. This can be avoided by cooling the mill.

7. Purity required:

Various mills used for size reduction often cause the grinding surfaces to wear off and thus impurities come in the powder. If a high degree of purity is required, such mills must be avoided. Moreover, the mills should be thoroughly cleansed between batches of different materials to maintain purity.

8. Physiological effect:

Some drugs are very potent. During their particle size reduction in a mill, dust is produced which may affect the operator. In such cases; the enclosed mills may be used to avoid dust.

9. Ratio of feed size to product size:

To get a fine powder in a mill, it is required that a fairly small feed size should be used. Hence it is necessary to carry out the size reduction process in several stages, using different equipment e.g. Preliminary crushing followed by coarse powder and then fine grinding.

10. Bulk density:

The output of the size reduction of material in a machine depends upon the bulk density of the substance.

Size Reduction Equipment Used

Equipment Used in Size Reduction:

1. Hammer Mill

Hammer Mill Principle:

• It works on the principle of impact that is the material is more or less stationary and is hit by an object moving at a high speed.
• The main mechanism involved is pulverization or grinding of the materials.

Hammer Mill Construction:

The hammer mill consists of three basic parts as follows

• Hopper, which delivers the material.
• The grinding mechanism usually consists of a rotor and stator.
• The discharging chute.

A hammer mill consists of a steel drum containing a vertical or horizontal rotating shaft or drum on which hammers are mounted. The hammers swing on the ends of the cross freely or fixed to the central rotor. The rotor rotates at a high speed inside the drum while the material is fed into a feed hopper. The material is impacted by the hammer bars and expelled through screens.

Hammer Mill Working:

The hopper containing material is connected to the drum.

• The material is powdered to the desired size due to the fast rotation of hammers and is collected under the screen.
• This mill has the advantage of continuous operation because the chance of jamming is less as the hammers are not fixed. ‘
• The mill can produce coarse to moderately fine powder. Due to the high speed of operation, heat is generated which may affect thermo labile drugs or material.
• Moreover, high speed of operation also causes damage to the mill if foreign objects such as stone or metal is present in the feed

Hammer Mill Uses:

•  It is used in pharmaceutical industries to process wet or dry granulations and disperse powder mixtures.
•  It is used in milling pharmaceutical raw materials, herbal medicine, and sugar.
• It is used in the powdering of barks, leaves, and roots of medicinal plants.
• It is applied in the milling of active pharmaceutical ingredients (API), excipients, etc

Hammer Mill Advantages:

It produces a specified top size without the need for a closed-circuit crushing system.

• Produces relatively numerous size distributions with a minimum of fines due to self-classification.
• It has a high reduction ratio and high capacity whether used for primary, secondary, or tertiary grinding.
• Relatively reasonable energy requirements.
• Brittle materials are best fractured by impact from blunt hammers.
• It is capable of grinding many different types of materials.
• The machine is easy to install and operate and its operation is continuous.
• It occupies a small space.
•  It is easy to maintain and clean.
• It is inexpensive
• It is easy if the manufacturer allows easier local construction.

Hammer Mill Disadvantages :

• Not recommended for the fine grinding of very hard and abrasive material due to excessive wear.
• Not suitable for low-melting sticky or plastic-like material due to heat generation in the mill head as a result of mill fouling.
• The mill may be choked if the feed rate is not controlled, leading to damage.
• The presence of foreign materials like stone or metals which finds its way into the material due to inadequate garbling process
• There is the possibility of clogging of the screen.

2. Ball mill

Ball mill Principle:

It works on the principle of impact and attrition.  Size reduction is done by impact and attrition as the balls drop from near the top of the shell.

Ball mill Construction:

A ball mill also known as a pebble mill or tumbling mill is a milling machine that consists of a hollow cylinder containing balls; mounted on a metallic frame such that it can be rotated along its longitudinal axis.

• The balls which could be of different diameters occupy 30 -50% of the mill volume and its size depends on the feed and mill size.
• The large balls tend to break down the coarse feed materials and the smaller balls help to form the fine product by reducing void spaces between the balls.
• Ball mills grind material by impact and attrition.

Ball mill Working:

The material is- put into a cylinder and it is rotated. The maintenance of the speed of rotation is important. At low speed, the balls will roll over each other and the size reduction will not occur at optimum level. At high speed, the balls will stick to the walls of the cylinder and no size reduction will occur. But at optimum speed, the balls will just taken up to the top and they will fall down.

Ball mill Uses:

The mill is used to grind brittle drugs to fine powder.

Ball mill Advantages:

1. It produces very fine powder (particle size less than or equal to 10 microns).
2. It is suitable for milling toxic materials since it can be used in a completely enclosed form.
3. It can be used for continuous operation.
4. It is used in milling highly abrasive materials.

Ball mill Disadvantages:

• Contamination of product may occur as a result of wear and tear which occurs principally from the balls and partially from the casing.
• High machine noise level especially if the hollow cylinder is made up of metal, but much less if rubber is used.
• Relatively long time of milling.
•  It is difficult to clean the machine after use.
• It is a very noisy machine

3. Fluid Energy Mill

Fluid Energy Mill Principle:

It operates by particle impaction and attrition.

Fluid Energy Mill Construction:

• It consists of a loop of pipe, having a diameter of 20 to 200 mm depending on the height, and may be up to about 2 meter.
• In the mill, material is suspended and conveyed at high velocity by air or steam, which passes through nozzles of 100 to 150 pounds per square inch.
• This doesn’t have any moving parts.

Fluid Energy Mill Working:

A fluid or milling gas, usually air or inert gas. is injected as a high pressure jet through nozzles at the bottom of the loop. The powder particles in the mill are accelerated to high velocity. The kinetic energy of the air plus the turbulence created causes inters particle (particle-particle collision) and particle-wall contact resulting in particle size between 2 and 10.

Fluid Energy Mill Uses:

• This mill can be used for size reduction of heat-sensitive materials.
• It is used in cases where high purity is required.

Fluid Energy Mill Advantages:

• The very fine size of particles can be obtained by using this mill.
• Required particle size can be achieved by using the classifier.
• Contamination of product cannot occur.
• Heat-sensitive materials can be used

Fluid Energy Mill Disadvantages:

1. It is energy-consuming
2. It may require pre-processing of materials to achieve the desired size.

4 . Edge Runner Mill

Edge Runner Mill Principle:

The material is getting crushed due to the weight of the stones and the shearing force which gets applied during the movement of these stones

Edge Runner Mill Construction:

It consists of two heavy rollers and a bed of material in a pan. The rollers have a central shaft and they revolve on its axis.

• The rollers are mounted on a horizontal shaft and move around the bed. A mill using more than two rollers is called a Chilean mill.
• The edge runner mills with perforated bottoms are known as grate mills.
• The scrappers are used for directing the material back to the center of the pan.
• Rollers are at the same distance from the center of the pan.

Edge Runner Mill Working:

The material to be ground is put in the pan and with the help of the scrapers it is kept in the path of the rollers. The material is ground for a definite period and then it is passed through the sieves to get powder of the required size.

Edge Runner Mill Uses:

It is used for size reduction of drugs to a fine powder.

Edge Runner Mill Advantages:

• It is mostly used for all types of drugs.
• Very fine particle size is produced.
• The major advantage of this mill is that it requires less attention during operation.
• The various groups of elements and combinations of such elements produce a machine that operates with greater efficiency.

Edge Runner Mill Disadvantages:

• It is not used for sticky materials.
• The process is noisy.

5. End Runner Mill

End Runner Mill Principle:

The material is getting crushed due to the weight of the heavy pestle and the shearing force that get applied during the movement of these stones.

End Runner Mill Construction and Working:

• It can be considered as a mechanical mortar and pestle, where the mortar is shallow and the bottom of the pestle is flat rather than round.
• It consist of bed of stone or mild steel with an eccentrically placed, vertical cylindrical dumb bell-shaped roll supported by a horizontal shaft such that when the shaft is rotated, friction between contacting surfaces of the bed and stone results in rotation of the roll and grinds the material placed on the bed.
• A scraper forces the material to the grinding surface. It can be used for size reduction of crystalline or brittle material.

End Runner Mill Use:

It is suitable for fine grinding.

End Runner Mill Disadvantage:

End runner mill is not suitable for drugs, which are in unbroken or slightly broken conditions.

Size Reduction In Pharmaceutical Engineering Multiple Choice Questions

Question 1. Size reduction cannot be obtained by

1. Flocculation
2. Physical
3. Mechanical
4. Precipitation

Answer: 1. Flocculation

Question 2. Size reduction of potent drugs is necessary due to one of the quality control parameters, in tablet formulation

1. Content uniformity
2. Friability
3. Hardness
4. Poor mixing

Answer:  1. Content uniformity

Question 3. Size reduction of material has the following disadvantage

1. High degradation
2. High dissolution
3. High flow of material
4. High surface area

Answer: 1. High degradation

Question 4. Which are the modes observed in ball mills?

1. Attrition and cutting
2. Cutting and compression
3. Compression and impact
4. Impact and attrition

Answer: 4. Impact and attrition

Question 5. Which mill includes a screen as an integral part of size reduction?

1. Ball mill
2. Edge runner mill
3. Colloid mill
4. Hammer mill

Answer: 4. Hammer mill

Question 6. Which one of the following is not true in the case of the construction of a hammer mill?

1. Hammers are flat or sharp edges
2. Metal sheet with holes or slots
3. Hammers are a swing or rigid type
4. Woven type of screen

Answer: 4. Woven type of screen

Question 7. If the given material is fibrous which mill will you prefer?

1. Ball Mill Colloid Mill
2. Colloid mill
3. Fluid Energy Mill
4. Cutter Mill

Answer: 4. Cutter Mill

Question 8. Which principle operates in the hammer mill?

1. Attrition
2. Cutting
3. Crushing
4. Impact

Answer: 4. Impact

Question 9. Which one of the following is not a size reduction process?

1. Clarification
2. Comminution
3. Diminution
4. Pulverization

Answer: 1. Clarification

Question 10. Sterile products cannot be obtained by

1. Ball mill
2. Colloid mill
3. Fluid energy, mill
4. Cutter mill

Answer:  4. Cutter mill