Drying
It is defined as the removal of small amounts of water or other liquid from a material by the
application of heat. Drying is possible when the environment is unsaturated with the water
vapour. Hence humidity is an important determinant for drying of solids.
The application of external heat to speed up the evaporation process is common practice in
drying. The application of vacuum allows moisture withdrawal at lower temperatures.
The circumstances of drying and moisture content are highly influential on the properties of
substances (e.g. density, adhesiveness, flow property, stability), making drying an important
operation in medicine manufacturing. In pharmaceutical technology drying can be an
intermediate (e.g. adjusting moisture content before granulation) or finishing (e.g. drying
the film coating) operation in the technological row.
Theory of drying
Drying can be described by three processes operating simultaneously:
1. Energy transfer from an external source to the water or organic solvent (Direct or
Indirect Heat Transfer). Rate of drying depends on the effectiveness of the contact
between wet materials with the hot surfaces.
2. Phase transformation of water/solvent from a liquid-like state to a vapour state
(Mass Transfer). Mass transfer in the solid as a liquid and vapour, and as a vapour
from the exposed surfaces. Movement within the solid results from a concentration
gradient which is dependent on the characteristics of the solid.
3. Transfer of the vapour generated away from the API and out of the drying
equipment (pressure/vacuum).
Applications of Drying
1. Preparation of bulk drugs: Example: Dried aluminium hydroxide, Spray dried lactose,
powdered extracts.
2. Preservation of drug product: Drying is necessary to avoid deterioration. Example:
➢ Crude drugs of animal & vegetable origin, synthetic & semi synthetic drugs, aspirin &
penicillin's tablets are undergoing chemical decomposition process.
➢ Blood products, skin & tissue undergo microbial decomposition.
3. Improved characteristics: Drying produces material of spherical shape, uniform Size,
free flowing & enhanced solubility. Example: Granules are dried to improve the
fluidity & compression characteristics.
4. Improved handling: Removal of moisture makes the material light in weight &
reduces the bulk; thus the cost of transportation will be less & storage will be
efficient.
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Non thermal drying
➢ Expression: The expression of solid to remove liquid. e.g. Squeezing of wetted
sponge
➢ Extraction: mixture is brought into contact with a solvent in which the substance of
interest is soluble, but the other substances present are insoluble.
➢ Absorption: The absorption of moisture from gases by passage through a sulfuric
acid column.
➢ Desiccation: Desiccation of moisture from a solid by placing it in a sealed container
with a moisture-removing material e.g. silica gel in bottle.
Moisture content of wet solids
Total moisture content: the total amount of liquid associated with a wet solid.
The moisture content of a wet solid is expressed as kilograms of moisture associated with 1
kg of the moisture free solid. Thus moisture content of 0.4 means that 0.4 kg of removable
water is present per kg of the solid. It is sometimes calculated as percentage moisture
content.
Unbound water: It is the amount of water held by the material that exerts a vapor pressure
equal to that of pure water at the same temperature. It can be removed readily by
evaporation. During a drying process this water is easily lost but the resulting solid is not
completely free from water molecules.
Unbound water exists mostly in the voids of the solids. Thus, in a non hygroscopic material,
all the liquid is unbound water.
In a hygroscopic material, the unbound moisture is the liquid in excess of the equilibrium
moisture content.
Bound water: Part of the moisture present in a wet solid may be adsorbed on surfaces of
the solid or be adsorbed within its structure to such an extent to prevent it from developing
its full vapour pressure and from being easily removed by evaporation. Such moisture is
described as “bound” and is more difficult to remove than unbound water.
Free moisture content: The easily removable water of a wet solid.
Equilibrium moisture content (EMC): The moisture content present in a solid under steady-
state ambient conditions is termed the equilibrium moisture content. Its value changes with
temperature, humidity and the nature of the solid.
Desorption: When air is continuously passed over the solid containing moisture more than
EMC, then solid loses water continuously till EMC is reached. This phenomenon is known as
desorption.
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Sorption: When air is continuously passed over the solid containing moisture less than EMC,
then solid absorbs water continuously till EMC is reached. This phenomenon is known as
sorption.
Factors Affecting EMC
Nature of material
➢ Nonporous insoluble solids have an EMC zero. Example: Talc
➢ For fibrous or colloidal organic substances, EMC values are high.
➢ For porous solids, EMC values are much higher & variable.
Nature of Air
➢ For air of zero humidity, EMC of all materials is zero.
➢ As the temperature of air increases, the EMC of solid decreases.
Relative humidity (RH) of air
Air at a given temperature air is capable of taking up water vapour until it is saturated (at
100% RH). It is a simple solution of water in air that follows the rules of most solutions - such
as increased solubility with increasing temperature, a maximum solubility at a particular
temperature (saturation) and precipitation of the solute on cooling (condensation, rain). If
the temperature is raised then the air will be able to take up more moisture and the relative
humidity falls.
It should be noted that in convective drying, where warm air is passed over the surface of a
wet solid, the relative humidity may rise during the drying process as a result of two
separate factors:
i. Uptake of evaporated water vapour from the wet solid,
ii. The cooling of the supply air as it transfers heat to the wet solid (evaporative
cooling).
Relationship between equilibrium moisture content (EMC) and relative humidity
The EMC of a solid exposed to moist air varies with the relative humidity. Ordinary
atmospheric conditions are of the order of 20°C and 70-75% RH.
Materials exposed to humid conditions will regain moisture, and so there is no advantage in
drying to moisture content lower than that which the material will have under the
conditions of use.
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Loss of water from wet solids
Unbound water is easily lost by evaporation until the equilibrium moisture content of the
solid is reached. Once the solid reaches its EMC, extending the time of drying will not
change the moisture content as an equilibrium situation has been reached. The only way to
reduce the moisture content is to reduce the RH of the ambient air. This can be done
mechanically with an air-conditioning system.
On small scale, desiccators are used.
Types of drying method
The following points should be considered before the selection of the suitable drying
method:
➢ Heat sensitivity of the material being dried.
➢ Physical characteristics of the material.
➢ Nature of the liquid to be removed.
➢ The scale of the operation.
➢ Available sources of heat (steam, electrical).
The general principles for efficient drying can be summarized as follows
✓ Large surface area for heat transfer.
✓ Efficient heat transfer per unit area (to supply sufficient latent heat of vaporization
or heat of sublimation in case of freeze-drying)
✓ Efficient mass transfer of evaporated water through any surrounding boundary
layers, i.e. sufficient turbulence to minimize boundary layer thickness.
✓ Efficient vapour removal, i.e. low relative humidity air at adequate velocity.
Drying rate curve
It is obtained by plotting time/moisture content on X- axis & drying rate on Y- axis.
Depending on external conditions & internal mechanism of fluid flow, solids show different
drying patterns.
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1. Initial Adjustment Period: It is time corresponding to AB curve, which is also called as
‘Heating up Period’. A wetted substance when kept for drying it absorbs heat from
surrounding & vaporization of moisture takes place which cools the surface. Heat flows to
the cooled surface at higher rates, leads to rise in temperature and evaporate again.
This continues & after some time heating & cooling rate becomes equal. This is referred by
the point B on graph.
2. Constant rate period: It is time corresponding to BC curve in graph. The temperature
remains constant & rate of drying is constant. During this period, there is a continuous liquid
film over the surface of solid. Moisture evaporating from the surface is replaced by the
water diffusing from the interior of the solid.
Rate of diffusion = Rate of evaporation
As drying proceeds, solid surface fails to maintain uniform film and drying rate start falling.
Point (point C) at which decrease in drying rate starts is referred to as the critical moisture
content (CMC).
3. First falling Rate period: It is time corresponding to CD curve. During this period, surface
water is no longer replaced at a rate fast enough to maintain a continuous film on the
surface. The area over which moisture film is not present is known as ‘dry spot’. Dry spots
begin to appear & rate of drying begins to fall off. The point D is referred to as second
critical point.
4. Second falling rate period: It is time corresponding to DE in graph. During this period,
rate of drying falls even more rapidly than the first falling rate & no film is present on
surface.
At the end, the drying rate becomes zero & moisture content of solids at this point (Point E)
referred to as Equilibrium Moisture Content (EMC).
Classification of dryers
A) Based on solid handling
➢ Static: The object to dry is placed on a tray. It does not move in relation to other
drying objects.
➢ Agitated: The drying items (usually a granulate or particulate) are mechanically
mixed to enhance exposure to the hot surface and drying homogeneity.
➢ Fluidized: The objects to dry (usually fine particulates) are suspended in the drying
media to maximize the drying area.
B) Based on the processing
➢ Batch: small quantities/ long residence time.
➢ Continuous: large quantities/small residence time.
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C) Based on mechanisms of heat transfer
➢ Direct (convection)
➢ Indirect (conduction)
➢ Radiant (radiation)
➢ Dielectric or microwave (radio frequency) drying
Direct/adiabatic dryer (convective type): are the types where the solids are dried by direct
contact with gases. More than 85% of the industrial dryers are of the convective type.
Indirect/non-adiabatic dryer (conductive type): Heat transfer to the product is
predominantly by conduction through the metal wall and the impeller.
Tray dryer
In the tray dryer, hot air is continuously circulated. Forced convection takes place to remove
moisture from the solids placed in trays. Simultaneously, the moist air is removed partially.
This is also called as shelf, cabinet or compartment dryer.
Construction: Tray dryer is a double walled cabinet with Single or Two doors. The gap
between two walls is filled with high density fibre glass wool insulation material to avoid
heat transfer. Doors are provided with gaskets. Stainless steel trays are placed on top of
each other in trolleys. Tray dryer is available in capacities ranging from 6, 12, 24, 48, 96, 192
trays.
Principle: The materials to be dried are placed in the trays. Heat transfer is by circulation of
hot air by electric heaters or steam in radiator coils. Blower fans are installed inside to
ensure proper circulation and transfer of heat. A control panel to control the temperature
and other parameters is fixed outside the dryer.
A highly effective recirculating air system is provided. The heated air is recirculated with
fresh air in selected proportions for optimum drying. The system is designed so that the
materials at the top and the bottom dry simultaneously.
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Advantages: The main advantage of tray dryers, apart from their low initial cost, is their
versatility. With the exception of dusty solids, materials of almost any other physical form
may be dried.
They are flexible, easy to use and the drying progress can easily be monitored, which makes
them beneficial for laboratory drying.
Disadvantage:
➢ It requires more labour to load & unload
➢ Drying times are typically long (usually 12 to 48 h).
Rotary/Drum dryer
Construction: It consists of a horizontally mounted hollow steel drum whose external
surface is polished. Below the drum, feed pan is placed in such a way that the drum dips
partially into the feed.
On one side of the drum a spreader is placed & on other side a doctor’s knife is placed to
scrap the dried material. A storage bin is placed connecting the knife to collect the material.
Working: Steam is passed inside the drum. Drying capacity is directly proportional to the
surface area of the drum. Heat is transferred by conduction to the material.
Drum is rotated at a rate of 1- 10 revolutions per minute. The liquid material present in the
feed pan adheres as a thin layer to the external surface of drum during its rotation.
Material is completely dried during its journey in slightly less than one rotation. The dried
material is scrapped by knife, which then falls into a storage bin. The time of contact of the
material with the hot metal is 6-15 seconds only.
Advantages
➢ Heating time is less only few seconds. Hence, heat sensitive material can be dried.
➢ The equipment is compact, occupying much less space than other dryers.
➢ The method gives rapid drying, the thin film spread over a large area resulting in
rapid heat and mass transfer.
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Disadvantages: operating conditions are critical and it is necessary to introduce careful
control on feed rate, film thickness, speed of drum rotation and drum temperature.
Spray Dryer
Principle: The spray dryer provides a large surface area for heat and mass transfer by
atomizing the liquid to small droplets. These are sprayed into a stream of hot air, so that
each droplet dries to a solid particle.
The drying chamber resembles the cyclone ensuring good circulation of air, to facilitate heat
and mass transfer, and that dried particles are separated by the centrifugal action.
Construction: It consists of a large cylindrical drying chamber with a short conical bottom,
made up of stainless steel.
An inlet for hot air is placed in the roof of the chamber & another inlet carrying spray disk
atomizer is set in the roof.
Spray disk atomizer is about 300 mm in diameter & rotates at a speed of 3000 to 50,000
rpm. Bottom of the dryer is connected to a cyclone separator.
spray drying apparatus with different flow
spray dryer cyclone separator patterns
Working: Drying of material in spray dryer involves three stages.
a) Atomization of liquid: Rotary atomizer is preferable than jet which is easily blocked. Liquid
is fed to the disc of the atomizer which is rotated at high speed; a film is formed and spread
as uniform spray. In addition, the rotary atomizer is effective with suspensions. It can be
operated efficiently at various feed rates.
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Rotary atomizer Drying of liquid droplets
Rate of feed adjusted in such a way that droplets should be completely dried before
reaching walls of drying chamber.
b) Drying of liquid droplets: The products are uniform in appearance and have characteristic
shape, in the form of hollow spheres with a small hole. This arises from the drying process,
since the droplet enters the hot air stream, and dries on the outside to form an outer crust
with liquid still in the center. This liquid then vaporizes, the vapour escaping by blowing a
hole in the sphere.
c) Recovery of dried product: Centrifugal force of atomizer drives the droplet to follow
helical path. Particles are dried during their journey & finally fall at the conical bottom.
Advantages
1) The actual drying time of a droplet is only a fraction of a second, and the overall time
in the dryer is only a few seconds.
2) Because evaporation is very rapid, the droplets do not attain a high temperature,
most of the heat being used as latent heat of vaporization. It is most useful for drying
of thermolabile materials e.g. antibiotics.
3) The powder will have a uniform and controllable particle size.
4) The product is free-flowing, with almost spherical particles, and is especially
convenient for tablet manufacture.
5) Labour costs are low, the process is completed in a single operation with no
handling.
6) It is possible to operate spray driers aseptically using heated filtered air to dry
products such as serum hydrolysate.
7) Some spray driers operate in a closed-circuit mode with an inert gas to minimize
oxidation of the product. Volatile solvents can be recovered from such systems.
Disadvantages: The equipment is very bulky & expensive.
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Fluidized Bed Dryer
Principle: 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
will be blown up and become suspended in the air stream.
At the stage solid bed looks like the boiling liquid, therefore this stage is called as fluidized.
Use of hot air to fluidizing the bed will increase the drying rate of the material.
Working: Fluidized bed dryer contains a stainless steel chamber having a removable
perforated bottom known as the bowl. Material to be dry is placed in this bowl. Air is
filtered and heated at required temperature by the heaters; and then passes through the
bed of the material. The flow rate and the operating temperature are adjusted by the
control panel. This air is introduced with required velocity and temperature that the bed
gets fluidized allowing intimate contact of each particle with the air.
The particles in the bed are carried forward slowly along the length of the dryer. All the
moisture present in particles get sucked by the hot air which then escapes into the dust
recovery system (bags) and is recycled for the further use in process. The dried material is
then fed into the cooling zone where cool air reduces the temperature of the material to the
required state.
Advantages
1. Fluidized bed dryers guarantee fast (20 to 40 minute compared to 24hr of tray dryer)
and homogeneous drying
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2. It facilitates the drying of thermolabile substances, as contact time is short. This is
one of the main reasons why fluidization is common in most pharmaceutical
industries.
3. Fluidized bed ensures 99.9% efficiency in the drying process while saving thermal
heat. Thermal efficiency of fluid dryers is 3 times greater than those of other
conventional drying systems.
4. Handling fluidized bed dryer is easy and less labor intensive
5. Fluid bed dryer has Low maintenance cost hence, reduces downtime
6. No hot spots on the final products: When products are in direct contact with the
drying surface. The hot spot is a common phenomenon in most drying equipment.
7. Fluid bed dryer is suitable for both continuous & batch material processing
Disadvantages
1. Many organic powders develop electrostatic charge during drying. To avoid this,
efficient earthing of dryer is essential.
2. Drying sticky material is quite difficult
3. The turbulence of the fluidized state may cause excessive attrition of some
materials, with damage to some granules and the production of too much dust.
4. Fine particles may become entrained & must be collected by bag filters.
Uses
a) It can be used in three operations like mixing, granulation & drying.
b) It is modified for coating of granules.
Vacuum dryer
In vacuum dryer, material is dried by the application of vacuum. When vacuum is created,
the pressure is lowered so that water boils at a lower temperature. Hence, water
evaporates faster. The heat transfer becomes efficient i.e. rate of drying enhances
substantially.
Pressure is usually decreased to 30 – 60 kPa. As a result, evaporation of water takes place at
25 – 30 °C.
Construction: The vacuum oven consists of a jacketed vessel to withstand vacuum within
the oven. The oven can be closed by a door. The oven is connected through a condenser and
liquid receiver to a vacuum pump.
The enclosed space is divided into a number of portions by means of 20 hollow shelves,
which are part of jacket. Steam or hot air is supplied into the hollow space of jacket &
shelves. Over the shelves, metal trays are placed for keeping the material.
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Advantages
➢ Drying takes place at a low temperature.
➢ There is little air present, so, there is minimum risk of oxidation.
Disadvantages
➢ Limited capacity & used for batch process.
➢ More expensive than tray dryer. Labor & running cost is also high.
➢ There is danger of overheating as the material is in contact with steam heated
surface for longer period.
Uses
i. Heat sensitive materials, which undergo decomposition.
ii. Dusty & hygroscopic material.
iii. Drugs containing toxic solvents. These can be separated into closed containers.
iv. Feed containing valuable solvents. These are recovered by condensation.
Freeze Dryer or lyophilization
Freeze drying is the removal of ice or other frozen solvents from a material through the
process of sublimation and the removal of bound water molecules through the process of
desorption, generally under reduced pressure. The term ‘lyophilization’ describes a process
to produce a product that ‘loves the dry state.’
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Sublimation is the transformation of ice directly into a gas without passing through a liquid
phase. Sublimation drying consists simply of reducing both the temperature & pressure
below the triple point. The triple point temperature of water is 273.15 K (0.0098 °C) and the
pressure is 611 Pa (4.58 mm).
As a result, any heat transferred is used as latent heat and the ice sublimes directly to the
vapour state. The vapour so produced is quickly removed by using power exhaust system.
Basic Steps of Freeze Drying Process
1) Pretreatment: Pretreatment includes any method of treating the product prior to
freezing. This may include concentrating the product, formulation revision (addition
of excipients to reinforce the structure of freeze-dried products, Lyoprotectant bio-
membrane to protect proteins). This reduces the actual drying time.
2) Pre-Freezing: The performance of the overall freeze drying process depends
significantly on this stage. The material system to be processed is cooled down to a
temperature that is always below the solidification temperature of the material.
The objective of the freezing stage is to freeze most of the water originally present in the
product for its posterior sublimation.
3) Primary Drying: (Temperature = -10 to -30 °C, Pressure = 10 to 30 pa)
After the freezing step has been completed, the pressure within the freeze-dryer is reduced
using a vacuum pump. 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
where it is deposited as ice. The sublimation of water from the product requires energy
(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.
Ice was removed in this initial drying phase. About 95% of the water in the material is
sublimated. This phase may be slow (can be several days in the industry), the ice being
removed at a rate of about 1 mm depth/hour.
4) Secondary Drying: (Temp. = 20 to 40 °C for several hours, Pressure = 10 to 30 pa)
Secondary drying involves removal of water which did not freeze (bound water). In the area
where the ice has already been removed, desorption of water from the cake occurs; this
process is referred to as secondary drying and already starts in the primary drying phase.
Once all ice has been removed from all product containers, the shelf temperature is
elevated to break any physico-chemical interactions that have formed between the
water molecules and the frozen material.
Secondary drying times are usually designed to achieve a reduction of moisture content
within the cake to less than 1%.
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5) Packaging: In view of packaging of the freeze dried products, special care must be
done to ensure protection from moisture. After drying, the vacuum is replaced by
inert gases.
Containers should be closed without contacting the atmosphere, for example, ampoules are
sealed under vacuum. Or, the closure of containers must be carried out under controlled
atmospheric conditions.
Factors affecting the process rate
From the diagram it can be seen that the direction of heat and mass transfer causes the top
of the product to dry first with drying proceeding downward to the bottom of the vial.
Therefore, as drying proceeds, there exists a three-component or layer system in each vial:
➢ the upper dry product
➢ the middle sublimation front
➢ the lower frozen liquid product
Figure: Schematic of heat and mass transfer in the freeze dryer.
As the dried layer increases, it becomes a greater barrier or the source of greatest resistance
to the transfer of mass out of the vials. This point out the importance of vial dimensions and
volume of product per vial on the efficiency of the freeze-drying process. If large volumes of
solution must be processed, the surface area relative to the depth may be increased,
utilizing larger vials or by using such devices as freezing the container in a slanted position to
increase the surface area.
The actual driving force for the process is the vapor pressure differential between the vapor
at the surface where drying of the product is occurring (the drying boundary) and at the
surface of the ice on the condenser.
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Types of freeze dryers
There are essentially 3 categories of freeze dryers:
i. Rotary Freeze Dryers: Rotary freeze dryers are usually used with liquid products,
e.g. pharmaceutical solutions, tissue extracts.
ii. Manifold Freeze Dryers: Manifold freeze dryers are usually used when drying a large
amount of small containers.
iii. Cabinet Freeze Dryers: Cabinet freeze dryers are the most common, because they
can be used to dry a variety of materials.
Construction of Freeze Dryer
It consists of:
i. Drying chamber in which trays are loaded.
ii. Heat supply in the form of radiation source, heating coils.
iii. Vapor condensing or absorption system.
iv. Vacuum pump or steam ejector or both.
Application of Freeze Dryer
a) Pharmaceutical Industry: This method is applied only to biological products-
antibiotics (other than penicillin), blood products, vaccines (such as BCG, yellow
fever, small pox).
➢ Enzyme preparations – Hyaluronidase.
➢ Microbiological cultures.
b) Food Industry: Freeze dried ice cream, instant coffee etc.
c) Other Industry: Also frequently used in different technological industries. Very
recently, some taxidermies have begun use of freeze drying to preserve animals.
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Advantages of Freeze Dryer
1. Drying takes place at very low temperature, so that enzyme action is inhibited, and
decomposition particularly hydrolysis is minimized.
2. The solution is frozen so that the final dry product is a network of solid occupying the
same volume as the original solution. Thus the product is light and porous.
3. The porous form of the product gives ready solubility.
4. There is no condensation of the solution prior to drying. Hence, salts do not
concentrate or denature proteins, as occurs with other drying methods.
5. Under high vacuum, there is no contact with the air, thus oxidation is minimized.
Disadvantages of Freeze Dryer
1. Single most expensive unit operation.
2. The porosity, ready solubility, and complete dryness yield a very hygroscopic
product.
3. The process is very slow.
4. Packaging requires special attention/conditions.
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