Drying

 Chapter 7 

DRYING

INTRODUCTION

• Drying is a mass transfer process in which water, or another solvent is removed by evaporation from a solid, semi-solid or liquid. Drying is often a final step in production or packaging of pharmaceutical products. To material to be considered as "dried", the final product must be solid, in the form of a continuous sheet, long pieces, particles or powder. The drying process involves a source of heat and a facility to remove the produced vapours. In majority of pharmaceutical intermediates or finished products the solvent removed is water. Desiccation may be synonymous with drying or considered an extreme form of drying. In pharmaceutical industry final product quality is never be compromised. The deterioration of the product may be due to microbial infection, oxidation, and thermal decomposition, contamination by metallic particles or by presence of organic solvent. These solvents need to be removed at any cost.

• The materials used in construction of dryers should be non-contaminating and should be like polished stainless steel or enameled iron. Closed dryers are often useful when moisture removed is organic solvent or their mixture. The oxidative decomposition is prevented by performing drying in an inert gas. Thermal decomposition can be reduced by drying by vacuum and freeze-drying methods. All these requirements make dryers for pharmaceuticals use the most expensive.

• A variety of drugs are produced in pharmaceutical companies worldwide in many different forms and for that dryers need to operate at batch and continuous mode. The manufacturing of drug in solid forms such as tablets, capsules etc. is carried out in three subsequent stages namely synthesis of intermediate products, final synthesis of the drug and manufacture of dosage form. After each stage the products are dried. Selection of a proper dryer for these products depends on the properties of materials. Adjustment and control of moisture levels in solid materials through drying is a critical process in the manufacture of products. Drying of solid materials is one of the most common and important unit operation in the pharmaceutical industries, where powders and granules handled and manufactured. 

• The effectiveness of drying processes has a large impact on product quality and process efficiency. For example, in the batch processing of pharmaceuticals drying is a key manufacturing step. The drying process can impact subsequent manufacturing steps such as tableting or encapsulation and can affect critical quality attributes of the finished products. Apart from drying of solids for a subsequent operation, it may be carried out to improve handling characteristics such as bulk powder filling and powder flow. 

OBJECTIVES 

• The drying unit operation is used extensively in the pharmaceutical industry, but often a lack of understanding of the impact of the presence of moisture, environmental conditions and drying process parameters on active pharmaceutical ingredients critical quality attributes can create challenges during product development, manufacturing, storage and use. Thus, following are the objectives of drying:

• To overcome common challenges in pharmaceutical drying development, including material constraints for scale-up studies and transferring to different equipment types and sizes. 

• To understand drying development related to chemical and physical stability, drying kinetics, and powder properties and highlights common development gaps for improving drying development workflows within the industry. 

• To encourage further fundamental research and technological advancements for improving the drying process. 

• Other objectives are to carry out size reduction, to avoid deterioration on storage, to dry the tablet granules to reduce the moisture, to reduce the bulk and weight to lower transportation charges and for certain preparations such as spray dried lactose.

• To design and produce a dryer that conserves energy consumption for optimal utilization in terms of acquisition and operating cost and with optimal local content and versatility. 

• To understand the impact of factors and establish the product specifications, as well as the nature and limits of residual solvents, in agreement with current regulations. 

APPLICATIONS

In manufacturing of pharmaceuticals, the last stage of processing is drying which is carried out for one or more of the following applications:

• Drying is used to remove excess moisture or other volatiles from coatings and various substrates. 

• It is used to reduce and control moisture levels in solid materials in the manufacture of many materials. It is most important in the processing of highly thermolabile products which are not stable in liquid form. The lyophilization enables longer shelf life of thermolabile materials and make them suitable for storage and transport of the product. For example, drying of biological products such as blood plasma, vaccines, enzymes, microbiological cultures, hormones and antibiotics

• Drying is used to make the material easy or more suitable for handling and processing. In the manufacturing of bulk drugs or for large scale production of synthetic drugs, drying is essential to get free flowing materials. For example, dried aluminium hydroxide, spray dried lactose etc. 

• It has applications in avoiding or eliminating moisture that initiates corrosion and decreases the product or drug stability. For example, to avoid deterioration or contamination of crude drugs of animal and vegetable origin, synthetic and semi synthetic drugs. 

• It is used to maintain and improve good properties such as flowability, compressibility etc. of a materials. For example, drying of fresh plants such as belladonna leaves, nux vomica before subjecting them to size reduction.

• It is used in the production of tablets and granules to improve tablet properties especially, compression of viscous and sticky material.

• Drying is used to improve solubility of materials by modifying their physical form. For example, milk and coffee extract is dried to convert them into instant soluble power form. 

• Drying is necessary to make material light in weight that help to reduce the cost of transportation of large volume materials (liquids). 

• Drying is used as the final step in evaporation, filtration, and crystallization and to preserve materials from environmental factors.

• Drying is used to maintain and improve shelf life of thermolabile and hydrolytic substances for longer period of time. It is necessary to avoid deterioration of blood products, skin and tissue that undergo microbial decomposition. 

• Drying significantly decreases rate of chemical reactions as well as chances of microbial attack or enzymatic actions and thus improves stability. 

MECHANISM OF DRYING PROCESS

• The process of drying does not mean only removal of the moisture, but the physical structure and the appearance of material has to be preserved. Drying is governed by the principles of heat and mass transfer. When a moist solid is heated to an appropriate temperature, moisture vaporizes at or near the solid surface. The heat required for evaporating moisture from the drying product is supplied by hot air or a gas. Drying involves diffusion in which the transfer of moisture to the surrounding medium takes place by the evaporation from the surface. As some of the moisture from the surface vaporizes more moisture is transported from bulk of the solid to its surface. This movement by diffusion of moisture in a solid takes place by a various mechanisms depending upon the nature and type of the solid and its state of aggregation. Wide variety of solids are handled for drying such as crystalline, granular, beads, powders, sheets, slabs, filter-cakes etc. The mechanism involved in moisture transport in those solids is classified as

1. Transport by liquid or vapors diffusion. 
2. Capillary action.
3. Pressure induced transport.  

• A specific mechanism that involves in drying a specific solid depends on its nature, pore structure and the rate of drying. More than one mechanism may come into play and dominate at different stages of drying of the same material. 

• There are various common terms used in designing of drying systems. Moisture content of a substance which exerts as equilibrium vapors pressure less than of the pure liquid at the same temperature is referred to as bound moisture. Moisture content of the solid which exerts an equilibrium vapour pressure equal to that of pure liquid at the given temperature is the unbound moisture. 

EQUILIBRIUM MOISTURE CONTENT

• The moisture contained in a material comprises all those substances which vaporize on heating and lead to weight loss of the sample. The weight is determined by a balance and interpreted as the moisture content. As per this definition, moisture content includes not only water but also other mass losses such as evaporating organic solvents, alcohols, greases, oils, aromatic components, as well as decomposition and combustion products. The moisture content is also called as moisture assays which is one of the most important analyses performed on most of the pharmaceutical products. Water activity measurements parallel to the moisture content is also an important parameter for quality and stability of pharmaceuticals.  

• The moisture in products can be present in different forms based upon type of bonding with solids. It is called ‘Free water’ when water is on the surface of the test substance and it retains its physical form, ‘Absorbed water’ when water is present in large pores, cavities or capillaries of the test substance and ‘Water of hydration’ occluded in lattice ions or water of crystallization coordinately bonded to ions.

• The moisture content of solid in excess of the equilibrium moisture content is referred as free moisture (water). It must be noted that during drying only free moisture is evaporated. The free moisture content (FMC) of a solid depends upon the vapour concentration in the air above solid surface. The moisture contents of solid when it is in equilibrium with given partial pressure of vapour in gas phase is called as equilibrium moisture content (EMC). Similarly, the moisture content at which the constant rate drying period ends, and the falling rate drying period starts is called critical moisture content (CMC). During the constant rate drying period, the moisture evaporated per unit time per unit area of drying surface remains constant and in falling rate drying period the amount of moisture evaporated per unit time per unit area of drying surface continuously decreases. 

• When the water vapour pressure of the air approaches the saturation water vapour pressure at the temperature of the gas, the EMC of materials rapidly increases. At these stages, the process undergone by the material is not only adsorption. Water vapour begins to condense within the pore structures of the materials. Theoretically, if the material is in contact with air that is 100 % saturated for a very long period, all pores of the material should be filled with the condensed moisture. The EMC that corresponds to that hypothetical state is called the saturation moisture content (SMC) of the material. But in practice the rate of this process becomes infinitesimally small at an EMC that is known as the capillary saturation moisture content (CSMC) and is often substantially less than the saturation moisture content referred to above. 

Measurements  

The moisture content is determined by several direct and indirect methods.

Direct Methods:

• The direct methods include mainly thermos gravimetric methods. The moisture content can be determined by an oven method directly. The solid is weighed and dried, then weighed again according to standardized procedures. In the Thermogravimetric method, moisture is always separated. Thus, there is no distinction made between water and other readily volatile product components. A representative sample must be obtained to provide a useful moisture content evaluation. Also, the moisture content of the product must be maintained from the time the sample is obtained until the determination is made by storing in a sealed container. Thermogravimetric techniques can be used to continuously measure the mass of a sample as it is heated at a controlled rate. The temperature at which water evaporates depends on its molecular environment. The free water normally evaporates at a lower temperature than bound water. Thus by measuring the change in the mass of a sample as it loses water during heating it is often possible to obtain an indication of the amounts of water present in different molecular environments. For many solids this method is mandatory particularly for granules. For granules the moisture content is measured by heating them in hot air oven at suitable temperature until weight becomes constant. For heat sensitive materials vacuum is applied in the oven to decrease the boiling point of liquid. 

Indirect Methods:

• Indirect methods are developed to determine the moisture content rapidly. For example, use of modern heating measurement methods like infrared, microwaves, ultrasound, and spectroscopy. These methods are developed due to requirements of rapid, non-destructive and precise moisture content determination. The indirect methods are generally faster than the direct methods for moisture determination. When done properly, the indirect methods can be accurate and precise. However, the accuracy and precision of the indirect methods depend on careful preparation and analysis of known standards to establish reliable calibration curves. Indirect methods require a large capital investment in equipment. Nevertheless, preparation of the standards and accurate calibration curves must be verified by a specific direct method to establish a reliable indirect method of instrumentation that can achieve accurate and precise predicted values. 

• The methods for moisture determination given in USP24 NF19 are the best, classical, and addresses only the determination of moisture content. The U.S.P. offers two methods for the determination of moisture content in solids:

1. Titrimetric (Karl Fisher titration)
2. Gravimetric (Thermal gravimetric analysis)

• Moisture content is used in a wide range of scientific and technical areas, and is expressed as a ratio, which can range from 0 (completely dry) to the value of the materials' porosity at saturation. It can be given on a volumetric or mass (gravimetric) basis. Moisture content is expressed as a percentage of moisture based on total weight (wet basis) or dry matter (dry basis). Wet basis moisture content is generally used. The moisture content is expressed by following formulae. 

• Based on the different forms of moisture present in the material the method used for measurement of moisture may estimate more or less moisture content. Therefore, for different pharmaceutical products Official Methods of moisture measurement have been given by agencies. 

• Example: Accurately 10 g of granules are transferred into a 4 g container and after drying the container with granules weighs 6.3 g. What is percent moisture content in the granules on wet basis. 

Applications of Moisture Content Determination 

• Accurate per cent moisture content is essential for maintaining stability of drug products. If a product is too moist or too dry, it may not be suitable to be administered and will not exert desired therapeutic effect. Most of the pharmaceutical products contain moisture. The per cent moisture content is seldom of interest. Rather, it shows whether a product intended for trade and production has standard characteristics such as storage ability, agglomeration, microbiological stability, flow properties, viscosity etc. The dry substance content, concentration or purity, compliance with quality agreements, therapeutic value of the product and legal conformity are other important issues. In addition, determination of moisture content has following applications: 

1. Freshness: Fresh products has specified characteristic features. Moisture induces changes in the state of solid. As they age and begin to degrade, some dry out and some pick-up excess moisture and begin to mold. 
2. Labeling: Pharmaceutical industries require a minimum or maximum percentage of moisture in certain products in order for them to be packaged and labelled. If they don't fit to these standards, the products cannot pass the quality standards and unfit for commercial release. For example, freeze dried products, hard gelatine capsules etc. 
3. Cost: In processed pharmaceutical products, the percentage of water can determine its final price. Generally, a product with more water will cost less.
4. Processing: The moisture has effect on the performance of excipients thus manufacturers and physicians need to know the moisture content of product to ensure that it is processed and packaged in a safe, stable way. 
5. Quality: Moisture content determines the way most product appropriate to administer, taste, feel and look. It is one of the important ways to measure product quality.
6. Shelf life: The physicochemical stability of bioactive agents alone and in combination with excipients is affected by moisture. Thus, shelf life of product depends on its moisture content at the time of packaging and rate of moisture gain during storage. Stability of products depends upon the per cent moisture in finished products.

RATE OF DRYING

• When a wet non-porous granular solid material is placed in a tray and dried with a carrier gas like air under constant drying conditions of velocity, temperature, humidity and pressure of air at the inlet, the experimental data can be plotted as drying rate vs. free moisture content or time. The obtained typical drying rate curve is divided into a constant rate period (AB), a first falling rate period (BC) and a second falling rate period (CD). The free moisture content at the end of the constant rate period (B) is known as CMC. During drying process, the moisture content is plotted based on the entire material. In general, at the start of drying process there is an unsteady state of warming-up period during which wet solid keep changing till the beginning of the constant rate period. 

• The drying rate curves are not smooth and continuous which indicates that the drying process involves a single mechanism throughout. In drying calculations, the water content in the wet solid is usually expressed on a dry weight basis, i.e., Kg of water/Kg of dry solid. 

DRYING CURVE 

• For each and every product, there is a representative curve that describes the drying characteristics for that product at specific temperature, velocity and pressure conditions. This curve is referred to as the drying curve for a specific product. Variations in the curve will occur principally in rate relative to carrier velocity and temperature. The curve is extremely valuable in understanding unusual behaviour associated with the drying of each unique product. Drying process can be divided in to three periods:  

1.  Constant drying rate period
2. First falling drying rate period
3. Second falling rate period

Constant Drying Rate Period:

• In a constant drying rate period, a material or mass of material contain much of water that liquid surface exists which dries in a similar fashion to an open-faced body of water. Diffusion of moisture from within the droplet maintains saturated surface conditions and as long as this lasts, evaporation takes place at constant rate. When a solid is dried under constant drying conditions, the moisture content (MC) typically falls. The graph is linear at first, then curves and eventually levels off. Constant rate drying period (B-C) will proceed until free moisture appears from the surface, the moisture removal rate will then become progressively less. At CMC the drying rate ceases and remains constant. During the constant rate period, the moisture from interior migrates to the surface by various means and is vaporized. 

• As the moisture content is lowered, the rate of migration to the surface is also lowered. If drying occurs at too high temperatures, the surface forms closely packed shrunken cells which are sealed together. This acts as a barrier to moisture migration and tends to keep the moisture sealed within. This condition is known as ‘case hardening’. The constant rate period is characterized by a drying independent of moisture content. During this period, the solid is so wet that a continuous film of water remain over the entire drying surface, and this water acts to lower the drying rate. The temperature of the wetted surface attains the wet bulb temperature.      

•     Web Bulb Temperature (WBT): WBT is the steady state temperature shown by the thermometer whose bulb is covered with a wet wick and from which water is evaporating into a high velocity air stream. The quantity of water evaporated is not high enough to alter the temperature and humidity of the air stream. The air is blown at high velocity (minimum 300 m/min) to cause evaporation of water from the wick. Evaporation requires latent heat. This heat comes from surface of glass bulb of thermometer. So the temperature of the glass bulb decreases. The heat comes from the temperature difference between Tw and Ta (large). It is the case of simultaneous heat and mass transfer. This heat is latent heat for phase change of water-to-water vapour.

Falling Rate Periods:     

• The constant rate period ends when the migration rate of water from the interior of the surface becomes less than the rate of evaporation from the surface. The period subsequent to the critical point is called ‘the falling rate period’. Following this point, the surface temperature rises, and the drying rate falls-off rapidly. The falling rate period takes a far longer time than the constant rate period, even though the moisture removal may be much less. The drying rate approaches zero at some equilibrium moisture content.

Drying in falling rate period involves two processes: 

1. Movement of moisture within the material to the surface.
2. Removal of the moisture from the surface. 

• The method used to estimate drying rates and drying times in the falling rate period depends on whether the solid is porous or non-porous. In a non porous material, once there is no superficial moisture, further drying can occur only at a rate governed by diffusion of bulk moisture to the surface. In a porous material other mechanism appears, and drying takes place in the bulk of solid instead of at the surface. 

First falling drying rate period  

• The moisture content at the end of the constant rate period (point c), is the ‘critical moisture content’. At this point the surface of the solid is no longer saturated, and the rate of drying decreases with the decrease in moisture content. At point C, the surface moisture film evaporates fully, and with the further decrease in moisture content, the drying rate is controlled by the rate of moisture movement through the solid.

Second falling drying rate period:

• Period C to D represents conditions when the drying rate is largely independent of conditions outside the solid. The moisture transfer may be due to any combination of liquid diffusion, capillary movement, and vapour diffusion.

Effect of Shrinkage: 

• A factor that often greatly affects drying rate is the shrinkage of the solid as moisture is removed. Rigid solids do not shrink appreciably, but colloidal and fibrous materials do undergo shrinkage. The most serious effect is development of a hard layer on the surface which is impervious to the flow of liquid or vapour moisture and slows down drying rate. In many materials, if drying occurs at too high temperature, a layer of closely packed, shrunken cells, which are sealed together, forms at the surface that presents a barrier to moisture migration. Another effect of shrinkage is to cause the materials to warp and change its structure. Sometimes, to decrease these effects of shrinkage, it is desirable to dry with moist air. This decreases the rate of drying so that the effects of shrinkage on warping or hardening at the surface are greatly reduced. 

DRYING EQUIPMENTS 

• Drying equipments are classified in different ways, according to design and operating features or based on mode of operation such as batch or continuous. In case of batch dryer the material is loaded in the drying equipment and drying proceeds for a given period of time, whereas, in case of continuous mode the material is continuously fed to the dryer and dried material is continuously discharged. In some cases vacuum may be used to reduce the drying temperature. Some dryers can handle almost any kind of material, whereas others are severely limited in the size and style of feed they can accept 

• Drying equipments also can be categorized according to the physical state of the feed such as wet solid, liquid, and slurry and the type of heating system i.e. conduction, convection, radiation. Heat may be supplied by direct contact with hot air at atmospheric pressure, and the water vaporized is removed by the air flowing. Heat may also be supplied indirectly through the wall of the dryer from a hot gas flowing outside the wall or by radiation.

• Dryers can also be classified on the basis of exposure of material to be dried. Dryers exposing the solids to a hot surface with which the solid is in contact are called adiabatic or direct dryers, while when heat is transferred from an external medium it is known as nonadiabatic or indirect dryers. Dryers heated by electric, radiant or microwave energy are also non adiabatic. Some units combine adiabatic and non- adiabatic drying; they are known as  direct-indirect dryers. They can also be categorized on the basis of energy efficiency. To reduce heat losses most of the commercial dryers are insulated and hot air is recirculated to save energy. Modern designs have energy-saving devices, which recover heat from the exhaust air or automatically control the air humidity. Computer control of dryers in sophisticated driers also results in important savings in energy

Tray Dryer

• Tray drying is a batch process used to dry materials that are liquid or wet cake. Tray drying works well for material that requires more gentle processing or cannot be atomized in an air stream due to viscosity. This dryer is well utilized for drying of the wet products like crude drugs, chemicals, powders or the granules, etc. It is the most conventional dryer used very widely and still being used where the moisture content is more and where the product has to be dried at low temperature for long hours.

Principle:        

• A laboratory oven is the elementary form of tray dryer which contains a cabinet with a heater at the bottom. The values of these ovens are very less because of its uncontrollable heat transfer or humidity. When we fit a fan in the oven, the circulation of the forced hot air gets started. This process is beneficial for reducing the local flour concentrations and also for increasing the heat transfer. In the direct circulation form the air is heated and then focused on the object in a controlled flow. The material to be dried is dispersed on the tiers of the trays. For the circulation of the air across the drying materials, the screen in trays are perforated and lined with paper. A limited amount of heat is provided to every shelf at that time when the air passes over it to provide the latent heat of vaporization. This kind of dryers provides proper control of humidity and temperature.

Construction:

• Tray dryer can be electrically, or steam heated. It consists of any number of trays that varies with customer requirement. It is fabricated out of rigid angle iron frame with double walled panels insulated with best quality compressed fiber glass and with a rigid door fitted with strong hinges and best chosen locking system. There may be facility to circulate hot air such as fans. A control panel is fixed in the front of the oven to facilitate easy operation. It has a large functional space and is made of mild steel and in good finishing outside with synthetic enamel colour and inside painted with heat resistant paint to resist temperature up to 300 ºC. 

Working: 

• Tray dryer is widely used in pharmaceutical industries. The material to be dried is placed on the trays. The heat in the dryer is produced by the heater along a side or at base. Other than the hot air generated by the oven, the other method is to employ radiator coils that use steam for heat circulation. During the heating process the material to be dried is spread out on the trays. The heated air is directed to flow in a circulation form. It flows over the material in the trays in a controlled flow. Trays can have a solid, perforated or wire mesh base. A paper lining could be used to reduce chances of contamination through contact with the tray. The efficiency of the dryer depends on recirculation of the hot air. Apart from a regular supply and presence of heated air, it also depends on supply of fresh air. The fresh air is combined with the heated air in fixed proportion for an efficient performance. Such regulated drying is important to ensure uniform drying in the dryer at the bottom as well as at the top. Apart from the double-walled construction insulation is achieved by heating coils.

Advantages:

• It is operated on batch mode so each batch can be handled as a separate entity. 
• It is energy efficient dryer as it consumes less energy. 
• It’s simple to use and clean. 
• Tray dryer is available in different sizes thus capital cost can be controlled.
• Chamber walls are heated externally thus prevents condensation. 
• It is available in unique single chamber and multi chamber design with lowest leakage. 
• It has excellent surface contact between tray and shelf. 
• It is best option in small scale production and drying valuable pharmaceutical materials such as drying wet lumpy solids and wet cakes. 
• It has heavy duty hollow shelf design with all connection outside the chamber.
• Operating parameter can be controlled more easily.
• Using vacuum systems tray dryers can be best suited for drying of heat sensitive materials. 

Disadvantages: 

• As it is operated at low to intermediate temperatures the process is time-consuming. 
• Only a fraction of the solid particles is directly exposed. Heat transfer and mass transfer are comparatively inefficient. 
• It provides tendency to over-dry contents in the lower trays.
• The operation is long during cycle (5 to 45 h per batch) and expensive to operate due to high Laboure requirement for loading and unloading.
• Plastic substances can also be dried using this dryer.
• It is not suitable for large scale production.
• Thermolabile drugs, liquids, slurries, cannot be dried.

Applications: 

• Tray dryer has industrial applications such as in chemical and pharmaceuticals. 
• Sticky materials, granular mass or crystalline materials, precipitates and paste can be dried in a tray dryer
• It has been used in agricultural drying because of its simple design and capability to dry products at high volume.

Drum Dryer  

• The drum dryer has been used since long time for drying sheets of paper or cloth and, more recently, for drying liquids and pastes. Drum dryers in general and the various types of drum dryers (atmospheric single drum, vacuum single-drum, and the double-drum dryers) in particular are selected or rejected for any given drying requirement on the basis of their individual operating characteristics and costs.

Principle:

• Drum dryers operate by applying a thin layer of the product to be dried to the outside of a rotating drum. The drum is internally heated by steam which quickly evaporates any liquid from the product. After almost one full revolution the remaining dried material is removed from the drum by a knife as a film or powder.  

Construction: 

• Drum dryer is a moving bed dryer. The unit is constructed from cast iron and stainless steel, providing cleanliness and resistance to chemical attack. The drums are engineered with hard chrome plating or chrome plated over nickel to ensure maximum heat transfer and to accommodate high steam temperatures and pressures, precision machined to provide maximum and reproducible heat transfer throughout its life. The drums are hollow horizontally mounted 0.6 to 3.0 meter in diameter and 0.6 to 4.0 meter in length, whose external surface is smoothly polished. Steam or heating coils can be used inside the drum for heat generation. Heat is transferred by conduction to the material that can be controlled with a thermostat. Drum is rotated with a motor device at 1-10 p.m. 

• Double drum dryer: The extra capacity can be provided by using double drum dryer. A double drum dryer is also called as dual drum and is often used for products with low to medium viscosity. In this system, the product is fed into a pool between the two drums which always turn in opposite directions. The small space between the drums can be set accurately so that a desired film layer can be obtained. Other combinations are possible depending on the product and the desired end-result. 

• Vacuum drum dryer: A drum dryer that operates under vacuum allows the product to be dried at lower temperatures. These drum dryers provide a higher capacity and less product loss under vacuum. Two steam-heated drums turn in an air-tight casing under high vacuum. The liquid is fed between the drums from the top, dried and scraped-off before the drums have fully rotated. There is no accumulation of product residues and no recirculation of the material. The drum dryer is easily accessed for inspection and maintenance. There is a wide range of applications, including damage prevention to heat-sensitive product components or evaporation of solvents at low temperatures. The vapours collected are condensed elsewhere. Absence of atmospheric pollution and climatic conditions gives reproducible product quality. Feed materials can benefit from such careful treatment. Evaporation takes place within a few seconds without risk of oxidation. Thermolabile materials such as, enzymes and proteins are preserved and blockage of proteins is prevented. The end product can be dissolved easily into a liquid. Chemical products, too, can be processed in the dryer from using vacuum process and undergo the drying treatment. It can use a gas such as nitrogen to keep the environment inert. 

• Accessories: Dryers for pharmaceutical applications are generally provided with vapour canopy and extract system to remove the vapours from the operating area. Dryers for hazardous materials may be provided with complete dust and fume tight enclosures. 

Working: 

• Single drum dryer: The robust construction of drum dryers made them to be used efficiently over last 60 years and still are in use today. The drum body of the drum dryer is heated on the inside by steam. Steam heating gives a uniform temperature distribution over the drum surface to provide consistent product quality. The steam condenses on the inside of the drying drum. The condensate is continuously removed from the drum, so that the largest possible surface area remains available on the inside of the drum for condensation of 

• The steam system is a closed system, which means that the product cannot come into contact with the steam or condensate. Depending on the design of the drum dryer, the product is applied continuously as a thin film on the underside or top of the main drum. As the drum turns it is heated on the inside and the product dries on the outside of the drum dryer. The short exposure to a high temperature reduces the risk of damage to the product. The water or solvent evaporates and leaves from the surface of drum. If necessary, the vapour can also be suctioned-off locally around the drum. The dried product layer finally reaches the knife and is scraped-off. 

• Double drum dryer: The liquid to be dried is fed into the valley created by the two drums, where it is applied to the drums as they rotate together. The dry product is removed by a knife on each drum. Wet materials are completely dried during slightly less than one rotation from one side to another side of the drum. Dried materials are scrapped by a knife, which then falls into a product receiver. Contact time of the material with hot metal is 6 to 15 seconds only. Therefore, processing conditions such as film thickness and drum temperature are closely monitored and controlled. The shaft-mounted main drive speed is adjusted by electronic inverter in the control panel. The liquid or paste material present in the feed pan adheres as a thin layer to the external surface of the drum during its rotation.

• Product Removal: Product is removed from the drum dryer surface by means of an alloy steel doctor blade or knife rigidly clamped in a cast iron knife bar assembly. The knife is applied to the surface of the drum by pneumatic cylinders located at each end of the dryer. For improved knife life and reduced drum maintenance an oscillating knife system is fitted with either conventional or disposable knives. After removal from the drum the product is collected by a transverse screw conveyor specially designed to break up the product film or flakes into easy-to-handle particles. For products that may require cooling after removal from the drum air.      

Advantages: 

• Drum dryer gives a rapid (few seconds) drying and its mass transfer rate is higher. 

• The entire material is continuously exposed to uniform heat. This process is characterized by short drying time and minimum product heating. 

• The equipment is compact 100% closed system and tailored models are available. 

•  Their simple operation makes them run with the minimum of training and require no specialist maintenance. 

• Drum dryers are economical with cheap installation and 24 hour a day continuous production. 

• It can have vacuum facilities to prevent dust emission thereby giving a guarantee of optimal hygiene during the complete production process. 

• This dryer work with minimum energy consumption and does not require large dust recovery systems such as filters. 

• The heat is transferred by steam to the (metal) wall, which in turn transfers it to the product on the other side of the wall. All the heat transferred by the wall is used to dry the product and does not leave the machine or chimney unused making this dryer a much more efficient process. 

• Using these dryers' product supply can be controlled. Furthermore, drums create a kneading effect that prevents the formation of lumps in sticky products. 

• A perfect distribution over the entire length of the drum makes the system ideal for processing doughy or pasty products.

• The temperature of the drum can be controlled independently for the required drying task by setting the steam pressure and thus are best suited for processing certain heat-sensitive products,  

Disadvantages: 

• The operating conditions are critical and need to be monitored. 

• Skilled operators are needed to control feed rate, film thickness, speed of rotation and temperature.  

• It is not suitable for low concentration solutions or suspensions of low viscosity. 

Applications: 

• Drum dryer is used in drying of liquids and pastes of sticky and highly viscous products.

• It is used under vacuum for drying temperature sensitive products such as vitamins, proteins, yeasts, pigments, malt extracts, hormones and antibiotics. 

• It has closed process area that protects the product and/or the environment. 

• Drum dryer is used for drying solutions, slurries, suspensions etc.

• Used to dry products such as starch products, ferrous salts, suspensions of zinc oxide, suspension of kaolin, calcium, insecticides, barium carbonates etc. 

• Vacuum drum drying is used for instant beverages, chocolate products, chemicals and recovery of solvents, foods and beauty soaps etc. 

Spray Dryer      

• Spray drying is a method of producing a dry powder from a liquid or slurry by rapidly drying with a hot gas. This is the preferred method of drying of many heat-sensitive pharmaceuticals. A consistent particle size distribution can be achieved using spray drying of some industrial products such as catalysts.

Principle:

• Spray drying is the continuous transformation of feed from a fluid state into dried particulate form by spraying the feed into a hot drying medium. The feed is either solution, slurry, emulsion, gel or paste which is provided through pump in atomized form.

Construction:

• Many different types of spray dryers exist, each with different features for meeting various spray drying needs. A spray dryer consists of a feed pump, atomizer, air heater, air dispenser, drying chamber and systems for exhaust air cleaning and powder recovery/separator and process control systems. It consists of a large cylindrical drying chamber with a short conical bottom, made-up of glass (lab scale) or stainless steel (large scale). The diameter of the chamber is 2.5- 9 meters and height 25 meters or more. An inlet for hot air is placed in the roof of the chamber and another inlet carrying spray disk atomizer is set in the roof. The spray disk atomizer is about 300 mm in diameter and rotates at a speed of 3000 to 50,000 r.p.m. Bottom of the dryer is connected to a cyclone separator.

Working

• Spray drying is a one-step continuous unit operation that employs liquid atomization to produce droplets that are dried to individual particles when moved in a hot gaseous drying medium. The three stages that occur in a spray dryer before drying is accomplished include atomization, spray-air mixing and moisture evaporation and dry product separation from the exit air. The spray drying process begins with atomization. During atomization, a nozzle or rotary atomizer turns the liquid feed stock into small liquid droplets. This is followed by separation of the solute or suspension as a solid and the solvent into a vapour. It is during this stage that many of the desired product qualities such as particle size and viscosity are developed. When droplets exit the nozzles or atomizer, they are dried to form a powder which is easily packed and transported. Solids form as moisture quickly leaves the droplets. The solid is usually collected in a drum or cyclone. The nature of the final product depends on the design and operation of the spray dryer and the physicochemical properties of the feed. Drying of the powder is commonly completed using hot air. Final moisture content in the powder is controlled by adjusting the hot air temperature. The recovery process is last step that takes a few seconds to recover the powder from the exhaust gas within the cyclone.

Advantages:

• The main advantage of spray drying is its versatility of the technology. Spray drying offers multiple opportunities that no other single drying technology provides. The flexibility and reproducibility of spray dryer makes spray drying the process of choice for many industrial drying operations. It has following other advantages: 

• This technique has ability to operate in aseptic pharmaceutical processing. 

• Feed rates in spray drying can range from a few pounds per hour to over 100 tons per hour and thus can be designed to any capacity required. 

• The spray drying process is very rapid, with the major portion of evaporation taking place in less than a few seconds. 

• It is adaptable to fully automated control system that allows continuous monitoring and recording of very large number of process variables simultaneously.

• Wide ranges of equipment designs are available to meet various product specifications. 

• It has few moving parts and careful selection of various components can result in a system having no corrosion and wear and tear problems. 

• It can be used with both heat-resistant and heat sensitive products. 

• It can handle feed for drying in solution, slurry, paste, gel, suspension or melt form. 

• It can have control over properties such as particle size, bulk density, and degree of crystallinity, impurities and residual solvents. 

• It has ability to produce nearly spherical particles with uniform size and thus reduces the bulk density of the product. Powder quality remains constant during the entire run of the dryer.

Disadvantages: 

• The equipment is very bulky and the ancillary equipment components are expensive to install.
• The overall thermal efficiency is low, thus large volumes of heated air is wasted as pass through the chamber without contacting a particle. 
•  It is difficult maintain and clean after use. 
• It needs material in liquid form and thus solid materials cannot be dried using spray dryers. 
• Product degradation or fire hazard may result from product deposit in the drying chamber. 

Applications: 

Spray drying technology is widely applied in pharmaceutical fields as well as non-pharmaceutical fields. 

• Many pharmaceutical and biochemical products are spray dried, including antibiotics, enzymes, vitamins, yeasts, vaccines, and plasma. 

• It can be used for drying algae, antibiotics and moulds, bacitracin, penicillin, streptomycin, sulphathiazole, tetracycline, dextran, enzymes, hormones, lysine (amino acids), pharmaceutical gums, sera, spores, tableting constituents, vaccines, vitamins, yeast products, tannin products etc.

• Spray drying stands out as unique method in making granules and tablets. The composite particles with good compactibility and excellent micrometric properties as filler for direct tableting of controlled release matrix tablets. It has been used for granulating, for slow-release granulations of magnesium carbonate, theophylline and acetaminophen. The spherical composite particles consisting of amorphous lactose and sodium alginate are prepared by spray drying. 

•  It can be used in preparing dry powder aerosol formulations. For example, salbutamol sulphate particles prepared by spray drying, using a mini spray dryer and liposomal ciprofloxacin powder for inhaled aerosol drug delivery. 

• It can be used in preparing micro particles for the preparation of dried liposomes, amorphous drugs, and mucoadhesive microspheres, microcapsules, gastro-resistant microspheres, and controlled-release systems. 

• Spray drying has proved extremely useful in the coating and encapsulation of both solids and liquids. Spray-dried micro particles of theophylline were prepared with a coating polymer in an aqueous system. 

• Dry emulsions can be prepared by spray drying of various liquid. For example, o/w emulsions containing fractionated coconut oil dispersed in aqueous solutions of HPMC (solid carrier). 

•  It can also be used to prepare dry elixirs. For example, Flurbiprofen Dry Elixir. 

• Non-pharmaceutical applications of spray drying includes drying of various materials in food, chemical and ceramic industry. For example, detergents, soaps and surface-active agents, pesticides, herbicides, fungicides and insecticides, dyestuffs, pigments, fertilizers, mineral floatation concentrates, inorganic chemicals, organic chemicals, spray concentration (purification), milk products, egg products, food and plant products, fruits, vegetables, carbohydrates and similar products, slaughterhouse products, fish products and many others. 

FLUIDIZED BED DRYER

• Fluidized bed dryer (FBD) is well known and widely used equipment in the pharmaceutical manufacturing. It is used in granulation process for drying the material to get desired moisture content in the granules or powders required for perfect compression of tablet formulation. Conventional fluidized bed dryers include batch fluidized bed dryer, semicontinuous fluidized bed dryer, well-mixed continuous fluidized dryer and plug flow fluidized bed dryer.

Principle:

• The equipment works on a principle of fluidization of the feed materials. In fluidization process, hot air is introduced at high pressure through a perforated bed of moist solid particulate. If air is allowed to flow through a bed of solid powdered material in the upward direction with the velocity greater than the settling rate of the particles, the solid particles are blown-up and remain suspended in the air stream. At this stage, the solid bed looks like the boiling liquid; therefore, this stage is called as fluidized. Heat transfer is accomplished by direct contact between the wet solid and hot gases. Use of hot air for fluidizing the bed increases the drying rate of the material. The vaporized liquid is carried away by the drying gases. Sometimes to save energy, the exit gas is partially recycled.

Construction:

• A fluidized bed dryer contains a stainless-steel chamber having a removable perforated bottom known as the bowl. A typical FBD consists of the air handling unit, product container, exhaust filter, exhaust blower, control panel, air distribution plate, spray nozzle, and solution deliver. The appropriate choice of distributor used during drying process ensures uniform and stable fluidization. The pressure drops across the distributor must be high enough to ensure good and uniform fluidization.

Working: 

• Material to be dried is placed in the bowl type vessel. Air is introduced from the top and heated at required temperature by the heaters. The air is filtered through the filter and then passes through the bed of the material at the bottom. The airflow is generated by the fans fitted at the top of the equipment. The air flow rate and the operating temperature are adjusted by the control panel. As the flow of air increases, the bed expands and particles of powder start to rise up in a turbulent motion. The regular contact with air causes the material to dry. The air leaving the FBD passes through the filter to collect the fine particles of the material. Fluidized bed dryer has a high drying rate and the material is dried in a very short time. Material remains free-flowing and uniform. FBD bags have finger-like shape to increase the volume of the drying bed that helps to increase the drying rate and decrease the drying time. 

Advantages:  

• FBD has high rates of moisture removal due to excellent air-particle contact which results in high heat and mass transfer rates thus has fast and homogeneous drying. 

• High thermal efficiency is usually achieved if part of the thermal energy for drying is supplied by the internal heat exchanger.

• It has low capital and maintenance cost.  

• Minimum contact time for drying is best suited for heat sensitive products.

• FBD is highly efficient in material drying to desired level. 

• Handling FBD is easy due to simple system control panel and thus requires less labour. 

• FBD designs come in a wide range of capacities and sizes.

• It shows no hot spots on the final products. 

• It is suitable for both continuous and batch material processing.  

Disadvantages:

• The high pressure drop requires more energy to suspend particles. 

• Requires increased air handling due to extensive recirculation of exhausts air for high thermal efficiency operation. 

•  It has poor fluidization and low flexibility in operation, especially if the feed is too wet. 

• Not the best choice of equipment when organic solvents are to be removed during drying.

• Non-uniform product quality for certain types of materials. 

• There may be entertainment of fine particles. 

• It has high potential for attrition, and in some cases agglomeration of fine particles.

• The conventional hot air FBD is not a good choice of dryer when handling toxic or flammable solids since there is danger of fire or explosion of flammability limits are exceeded. 

• It has a possibility of product loss. 

• There are high chances of electrostatic force build-up.

Applications:

• Fluidized bed dryers are used in chemical, pharmaceutical, food, dairy, metallurgical, dyes and other process industries for drying of powders, mixing of powders and agglomeration of various materials such as powders, tablets, granules, coals, fertilizers, plastic materials etc. 

• This process being fast is used in granulation of pharmaceutical powders.

• Fluidized bed coaters are used widely used for coating of powders, granules, tablets, pellets, beads that are held in suspension by column of air. 

• FBD is used for several purposes, such as fluidized bed reactors (types of chemical reactors), solids separation, fluid catalytic cracking, fluidized bed combustion, heat or mass transfer or interface modification, such as applying a coating onto solid items. 

• The three types (Top spray, Bottom spray, Tangential spray) of FBD are mainly used for aqueous or organic solvent-based polymer film coatings. 

• Top-spray fluidized bed coating is used for taste masking, enteric release and barrier films on particles/tablets. Bottom spray coating is used for sustained release and enteric release and Tangential spray coating is used for SR and enteric coating products. 

• FBD is efficiently employed for applications in chemical, pharmaceutical, dyestuff, foodstuff, dairy and various other process industries with the spray dryers and granulation systems for effective drying, mixing, granulation, finishing and cooling of powdered substances.

• It has been preferred over rotary dryers for drying and cooling a wide range of polymer materials which require precise control of residence time and temperature for effective processing. 

• It is used for drying moist dibasic calcium phosphate anhydrous (DCPA). 

• It is suitable for the formulation, development and production of clinical materials. 

• The modified versions of FBD are used as precision granulators, top spray granulators, spray drying granulator and granulator coater. 

• Various types of modified fluidized bed dryers have been developed and are applied in many industrial processes to overcome some of the problems encountered while using conventional fluidized bed dryer and for a drying process. 

Batch Type FBD: 

• Reverse turning bed type: In this FBD, by turning the air dispersion plate (the reverse turning bed) in 90° direction with the control motor, all the dried material can be discharged at once.

• Rotating discharge type: Dried material is discharged by opening the discharge gate equipped at the side of the dryer. Since the perforated plate is used as the air dispersion plate, the air inside the equipment whirls and pushes the dried material out from the discharge gate. Example: Vertical FBD with granulating option

Characteristics of batch FBD:

• The residence period of the dried material can be controlled which results in uniform drying.

• It is most suitable in case where an accurate control of the residence period is required at the decreasing rate drying zone.

• Small destruction of particle occurs therefore suitable for granular or crystallized material. 

• Easy operation can be achieved by an automatic control of material feeding, drying discharging etc.  When multiple stage system is adopted, the exhaust air heat can be used efficiently.

Continuous Type FBD: 

• Residence time in any drying zone is dependent on length of the zone, the frequency and the amplitude of the vibration and use of dams. Heat transfer units such as tube or plate are built inside the equipment. These units supply 60-80 % heat necessary for drying.      

• Example: Horizontal vibrating conveyor fluid bed dryer 

Characteristics of continuous FBD:

• The materials with relative high moisture content can be dried. 
• At and after a second drying chamber piston flowability can be achieved by arranging numbers of the partition plates as per the required residence period. 
• The perforated plate at the fixed direction ensures easy discharging. 
• It causes small destruction of particles and thus are suitable for drying granules or crystalline materials.  bed dryers heating and cooling occurs in same unit.
• Each zone has independent control for temperature, dew point and velocity of air. 
• By adjusting the weir height for each zone, residence time can vary up to four-fold in the unit  

Vacuum Dryer

• Vacuum drying is a viable technology used successfully for many years in the pharmaceutical, food, plastics and textile industries. It is an indirect-heat dryer and best used for drying heat sensitive materials at comparatively low temperature. These materials are dried by applying vacuum to evaporate the water or solvent. The use of vacuum lowers down the environmental pressure and hence lowers the boiling point of solvents and hence this process is known as vacuum drying. The combination of heat and vacuum together is very effective source of the drying at relatively lower temperature. The moisture content in the material dried via vacuum dryers is comparatively lower to those of normal dryers without vacuum.

Principle: 

•   Vacuum drying is the mass transfer operation in which the moisture present in wet solid is removed by means of creating a vacuum. The principle involved is creating a vacuum to decrease the pressure below the vapors pressure of the water. With the help of vacuum pumps, the pressure is reduced around the substance to be dried. This decreases the boiling point of water inside that product and thereby increases the rate of evaporation significantly. The result is a significantly increased drying rate of the product. The pressure maintained in vacuum drying is generally 0.0296 –0.059 atmospheres and the boiling point of water is 25 - 30 °C. The vacuum drying process is a batch operation performed at reduced pressures and lower relative humidity compared to ambient pressure, enabling faster drying.

Construction:

• In the pharmaceutical industry vacuum dryer is also known as vacuum oven. Vacuum dryers are made-up of stainless steel or cast iron so that they can bear the high vacuum pressure without any kind of deformation. The oven is divided into hollow trays which increases the surface area for heat conduction. The oven door is locked air tight and is connected to vacuum pump to reduce the pressure. Heat is usually supplied by passing steam or hot water through hollow shelves.  

Working:

• The materials to be dried are kept on the trays inside the vacuum dryer and pressure is reduced by means of vacuum pump. The dryer door is tightly shut, and steam is passed through the space between trays and jacket so that the heat transfer occurs by conduction. Water vapors from the feed are sent into the condenser. After drying vacuum pump is disconnected and the dried product is collected from the trays. The reduced pressure lowers the heat needed for rapid drying. Drying temperatures can be carefully controlled and, for a major part of the drying cycle, the material remains at the boiling point of the wetting agent. Drying times are long, usually about 12 to 48 h. The heat is transferred to the material as it contacts the dryer’s heated surface, drying the material by conduction. 

Advantages: 

• Vacuum dryers offer low temperature drying of thermolabile materials and are suitable for solvent recovery from solid products containing solvents. 

• Materials can be dried in final containers or enclosures with removing large amount of moisture compared to normal dryers.

• Average drying temperature is much lower than normal standard dryers and the quality of dried material is much better than that of the normal dryers. 

• Drying action becomes faster as heat is easily transferred throughout the body of the dryers, due to its large surface area.

• A major advantage is its energy conservation. It requires less energy for drying, cutting down on the economic and environmental costs associated with drying a product for storage, sale or other purposes.

• Vacuum-drying processes also tend to work faster than other drying methods, cutting down on processing times. 

• Another advantage of drying materials using this dryer is that it is a less damaging drying process. Vacuum drying tends to retain the integrity of the original item without damaging it with heat.

• It is predominately a batch unit operation however it can be integrated as continuous process. 

• This equipment reduces risks to workers from vented fumes and particles that can usually make people sick or that force people to wear protective garments while operating other dryers. 

Disadvantages: 

• In general vacuum drying process is batch type drying process with low efficiency.
• Vacuum dryers are expensive in terms of its cost and there is requirement of skilled labor to operate it.
• Cost of maintenance is comparatively high. 
• Its upper temperature limit (typically about 600 °F) is lower than that of a direct-heat dryer. Thus the rate at which material temperature can be raised in a vacuum dryer is also limited. The vacuum pump is primarily responsible for the vacuum level inside the dryer. 

Applications: 

The following examples describes areas in which vacuum-drying is employed. 

• Type of industries: Vacuum drying equipment has many applications across most industrial sectors such as chemical, pharmaceutical, food and plastics. 
• Type of operation: It is typically used for batch operation as it removes water or removes and recovers solvents from a moist material. 
• Changing physical state: It can be used to change a material's molecular and physical chemistry (called a phase change) in specialized operations such as chemical reactions and polymer solid stating.
• Separation: It is typically used for separating volatile liquid by vaporization from a powder, cake, slurry, or other moist material. 
• Indirect heat drying: The heat is transferred to the material as it contacts the dryer's heated surface, drying the material by conduction. 
• Safety: With a vacuum dryer, ventilation does not require and personnel working near the dryer are safer. It is also possible to recover the precipitated moisture collected during the drying for further use. 
• Drying pharmaceuticals: It is used in the preparation of mouth-dissolving tablets and granules of nimesulide, camphor, crospovidone and lactose by a wet granulation. Camphor sublimes from the granules by exposure to vacuum. The porous granules are compressed to get superior tablets. 
• Drying proteins: Vacuum-drying overcome long processing times (typically 3–5 d), and the inherent steps in freeze drying that lead to instabilities in the protein structure. Due to the complex structural properties, proteins have a tendency to denature and undergo irreversible aggregation during various processing steps of freeze drying. Vacuum drying is used in the formulation of proteins as dry powders using mannitol as the bulking agent. 
• Drying bacteria: Normally, probiotic bacterial strains and starter cultures are dry-frozen to preserve them until use. It consumes a very high amount of energy and some bacterial strains do not survive temperatures below 0 °C. Thus, lowtemperature vacuum drying can be used to dry probiotic at moderate temperatures above 0°C without causing too much damage to the cell structure.
• Vaccines and other injectable: Freeze drying involves use of vacuum to produce pharmaceutical products. Freeze-drying is used to increase the shelf life of products, such as vaccines and other injectable. By removing water from the material and sealing the material in a vial under vacuum, the material can be easily stored, shipped, and later reconstituted to its original form for injection. 

Freeze Dryer 

• Freeze drying, also called lyophilization, is a process in which water is frozen, followed by its removal from the sample, initially by sublimation followed by desorption. The equipment used to dry solutions or suspensions at or below freezing points of liquids is called as freeze dryer or lyophilizer. This drying process utilized in the manufacture of pharmaceuticals and biologicals that are thermolabile or otherwise unstable in aqueous solutions for prolonged storage periods, but that are stable in the dry state. 

Principle:

• The main principle involved in freeze drying is a phenomenon called sublimation, where water passes directly from solid state (ice) to the vapour state without passing through the liquid state. Sublimation of water can take place at pressures and temperature below triple point of water (4.579 mm of Hg and 0.0099 ºC). 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 non-volatile solid, dried components of the original liquid. The concentration gradient of water vapour between the drying front and condenser is the driving force for removal of water during freeze drying.

Construction: 

• Generally, there are three types of freeze dryers. There are manifold freeze-dryer, the rotary freeze dryer and the tray style freeze-dryer. The components common to all of them are a vacuum pump to reduce the ambient gas pressure in a vessel containing the substance to be dried and a condenser to remove the moisture by condensation on a surface cooled to − 20 to − 80°C. The manifold, rotary and tray type freeze-dryers differ in the method by which the dried substance is interfaced with a condenser.

1. In manifold freeze-dryers a short usually circular tube is used to connect multiple containers with the dried product to a condenser. 
2. The rotary freeze-dryers have a single large reservoir for the dried substance. Rotary freeze-dryers are usually used for drying pellets, cubes and other pourable substances. The rotary dryers have a cylindrical reservoir that is rotated during drying to achieve a more uniform drying throughout the substance.
3. The tray freeze-dryers also have a single large reservoir for the dried substance. They usually have rectangular reservoir with shelves on which products, such as pharmaceutical solutions and tissue extracts, can be placed in trays, vials and other containers 

• A freeze dryer consists of a vacuum chamber wherein product to be dried are kept on shelves and capable of cooling and heating containers and their contents. A vacuum pump, a refrigeration unit, and associated controls are connected to the vacuum chamber.    

       

Working:

• Traditional freeze drying is a complex process that requires a careful balancing of product, equipment, and processing techniques. In this process water is removed from a product after it is frozen and placed under a vacuum, allowing the ice to change directly from solid to vapour without passing through a liquid phase. It is performed at temperature and pressure conditions below the triple point of liquid, to enable sublimation of frozen material. The entire process is performed at low temperature and pressure. Steps involved in lyophilization start from sample preparation followed by freezing, primary drying and secondary drying, to obtain the final dried product. The concentration gradient of water vapour between the drying front and condenser is the driving force for removal of water during lyophilization. The vapour pressure of water increases with an increase in temperature during the primary drying. Therefore, primary drying temperature should be kept as high as possible, but below the critical process temperature, to avoid a loss of cake structure.

• Pretreatment: In this stage product is treated for freeze concentration, solution phase concentration, preserve product appearance, stabilize reactive products, increase surface area, and decrease high vapour pressure solvents concentration prior to freezing. In many instances the decision to pre-treat a product is based on theoretical knowledge of freeze-drying and its requirements, or is demanded by cycle time or product quality considerations

• Freezing: During freezing stage the liquid sample is cooled down to − 40 to − 60 °C until pure crystalline ice forms from part of the liquid and the remainder of the sample is freeze-concentrated into a glassy state where the viscosity is too high to allow further crystallization. 

• Primary drying: In primary drying the ice formed during the freezing is removed by sublimation under vacuum at low temperatures, leaving a highly porous structure in the remaining amorphous solute that is typically 10% water. This step is carried out at pressures of 10−4 to 10−5 atmospheres, and a product temperature of – 45 to – 20 °C. The sublimation during primary drying is the result of coupled heat- and mass-transfer processes. 

• Secondary drying: This is last step wherein most of the remaining water is desorbed from the glass as the temperature of the sample is gradually increased upto 10 - 15 °C while maintaining low pressures. Ideally, the final product is a dry, easily reconstituted cake with a high surface area and low moisture content (below 5% w/w).

Advantages:

• Oxidizable substances are well protected under vacuum conditions. 

• Long drying period owing to 95%-99.5% water removal.

• Loaded quantities are accurate and has content uniformity. 

• Little contamination owing to aseptic process. 

• Minimal loss in volatile chemicals and heat-sensitive nutrient and fragrant components.  

• Minimal changes in the properties because microbe growth and enzyme effect cannot be exerted under low temperature. 

• Transportation and storage of thermostable products is possible under normal temperature. 

• Rapid reconstitution time, usually less than 10 sec.

• Constituents of the dried material remain homogenously dispersed.

• Sterility of product can be achieved and maintained. 

Disadvantages: 

• Removing volatile compounds may require high vacuum. 

• Most expensive unit operation.

• Stability problems such as low temperature stress are associated with individual drugs. 

• There are some issues associated with sterilization and sterility assurance of the dryer chamber and aseptic loading of vials into the chamber.

Applications: 

• Pharmaceutical companies often use freeze-drying to increase the shelf life of products, such as vaccines and other injectable. 

• By removing the water from the material and sealing the material in a vial under vacuum, the material can be easily stored, shipped, and later reconstituted to its original form for injection.

•  Freeze-drying is used to preserve biologicals and make it very light weight.

• It is used to preserve blood products in freeze-dried form. 

• It is used in chemical synthesis where products are often freeze dried to make them more stable, or easier to dissolve in water for subsequent use. 

• As freeze-drying can effectively remove solvents that can be used in bio-separations as a late-stage of purification procedure. 

• In addition, it is capable of concentrating substances with low molecular weights that are too small to be removed by a filtration membrane.