Theory of Drying – Pharmaceutical Engineering

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