Drying

• Drying is defined as the removal of small amounts of water

or other liquid from a material by the application of heat.
• In evaporation, the product obtained is either concentrated
solution or suspension or wet slurry. In drying, dry solid is
the product.
 Objectives
• To transform the product in the acceptable form which will be
useful for further processing.
• To reduce the transportation cost as drying reduces the
weight of product.
• To improve physical and chemical stability of product.
Generally presence of moisture increases the rate of
reactions. Also it increases the chance of microbial attack.
• To improve some characteristics like flow of powder from
hopper, compressibility and size reduction.
 Applications
• Preparation of bulk drugs
• In the preparation of bulk drugs, drying is the final stage of processing. A few eg’s are dried
aluminium hydroxide, spray dried lactose, powdered extracts. Drying step is essential after certain
operations such as crystallization and filtration.
• Preservation of drug products
• Drying is necessary to avoid deterioration
• Crude drugs of animal and vegetable origin – chemical decomposition
• Blood products, skin, tissue – microbial growth
• Synthetic and semisynthetic drugs – chemical decomposition
• Effervescent tablets (aspirin, penicillins) – chemical decomposition
• Improved characteristics
• Drying produces materials of spherical shape, uniform size, free flowing and enhanced solubility.
Granules are dried to improve the fluidity and compression characteristics. These are essential for
the production of tablets and capsules. Viscous and sticky materials are not free flowing. Drying
modifies these characteristics. Examples are male fern extract, malt extract and oleoresin.
• Improved handling
• Removal of moisture makes the material light in weight and reduces the bulk. Thus cost of
transportation will be less and storage will be efficient. If moisture is present, size reduction of
drugs is difficult. Drying reduces the moisture content.
 Mechanisms
Type of dryer and mechanism Examples Advantages Disadvantages
Static bed dryer Tray dryer and Attrition is not Only a fraction of the
Systems in which there is no relative Freeze dryer observed solid particles is
movement among the solid particles directly exposed
being dried, although there may be
bulk motion of the entire drying mass.
Moving bed dryer Drum dryer The entire Attrition is possible
Systems in which the drying particles material is
are partially separated so that they continuously
flow over each other . exposed to heat
source
Fluidized bed dryer Fluidized bed Solid-gas contact Attrition of particles
Systems in which the solid particles dryer is excellent, takes place
are partially suspended in an upward uniform drying
moving heated gas system.
Pneumatic dryer Spray dryer Efficient and
Systems in which drying particles are rapid drying
entrained and conveyed at a high
velocity gas stream
 Measurements & applications of Equilibrium Moisture content, rate of drying curve

• Air of constant temperature and humidity

is passed over the wet solid.
• After a long exposure, equilibrium is
reached.
• On attaining equilibrium, further exposure
will not alter moisture content in the solid.
• At this stage, vapour pressure of the wet
solids is equal to that of the surrounding
atmosphere.
• Hence there is no driving force for mass
transfer.
• Equilibrium moisture content (EMC) : It is
the amount of water present in the solid
which exerts a vapour pressure equal to the
vapour pressure of the atmosphere
surrounding it. The moisture content stops
gaining or losing moisture when its in
contact with air.
 Measurements & applications of Equilibrium Moisture content, rate of
drying curve

• The characteristics of air such as

temperature and humidity are maintained
constant. Depending on these conditions,
the solids may lose moisture (desorption)
or adsorb (sorption).
• Desorption : when air (of constant
temperature and humidity) is continuously
passed over the solid containing moisture
more than EMC, them solid loses water
(dry) continuously till EMC is reached.
This phenomenon is known as desorption.
• Sorption : when air (of constant
temperature and humidity) is continuously
passed over the solid containing moisture
less than EMC, then solid adsorbs water
continuously till EMC is reached. This
phenomenon is known as sorption.
Measurements & applications of Equilibrium
Moisture content, rate of drying curve
Measurements & applications of Equilibrium Moisture content, rate of
drying curve

• Application of EMC:
• EMC curve permits the selection of experimental conditions to be used for drying of
the product.
• EMC data can help determine how drying variables like relative humidity and inlet air
temperature affect moisture levels in a product. It can also help avoid unnecessary
drying, which can increase costs and reduce drying system capacity.
• Drying should be stopped when the moisture content reaches the level of the EMC
under the exposed conditions. Over drying can be avoided.
 Theory of drying

• In a wet solid mass, water may be present as bound water and

unbound water.
• Bound water (moisture) is the minimum water (moisture) held by
the material that exerts an equilibrium vapour pressure less than
the pure water at the same temperature. (adsorb and absorb).
(absorbs moisture from air)
• Unbound water (moisture/water on surface) is the amount of
water (moisture) held by the material that exerts an equilibrium
vapour pressure equal to that of pure water at the same
temperature. (not readily taken up and retaining moisture) if
moisture accumulates in a non-hygroscopic material, it can lead to
liquid water build up on the surfaces of material.
 Theory of drying

VP (wet mass) < VP (pure water)

VP (wet mass) = VP (pure water)

Hygroscopic - is the phenomenon of attracting and holding water molecules via either
absorption or adsorption from the surrounding environment, which is usually at normal or room
temperature

Non hygroscopic - They do not absorb moisture internally

Rate of drying curve
Rate of drying curve
Rate of drying curve

Diffusion is the movement of molecules from a region of higher concentration to a

region of lower concentration down the concentration gradient.
Rate of drying curve • 3)
• Time corresponding to CD represents
first falling rate period (unsaturated
surface drying).
• Surface water is no longer replaced at
a rate fast enough to maintain a
continuous film on the surface.
• Dry spots begin to appear and rate of
drying begins to fall off.
• Point D is referred to as the second
critical point.
• At this point, the film of surface
water is completely evaporated.
Rate of drying curve
• 4)
• DE = second falling rate period
• Rate of drying falls even more rapidly
than first falling rate.
• Rate of drying depends on rate of
diffusion of vapour of moisture to the
surface of the solid.
• Point E is equilibrium moisture content
(EMC)

• Beyond E, the drying rate is equal to

zero.
• Therefore, temperature and moisture
content remain constant. Beyond E,
continued drying is waste of time and
energy.
 Equipments used for drying

• Tray Dryer
• Drum Dryer
• Spray Dryer
• Fluidized Bed Dryer
• Vacuum dryer
• Freeze dryer
Tray Dryer
Principal:
• Hot air is circulated over
the material.
• Moisture is removed
from the material by
force convection.
• Simultaneously some
moist air of dryer is
continuously getting
replaced with fresh air.
Tray Dryer
Construction:
• Rectangular chamber with insulated walls.
• Trays are arranged inside heating chamber.
• Number of trays may vary with the size of the dryer.
• Dryers of the laboratory size may contain a minimum of
three trays, whereas dryers of industry size may
contain more than 20 trays.
• The distance between the bottom of upper tray and
surface of the substance loaded in the subsequent tray
must be 40 mm.
• Electric heaters are provided for heating.
• Fans are fitted in heating chamber in order to circulate
the hot air over all the trays.
• In the corner of the chamber direction vanes are
placed to direct air in the expected path.
Tray Dryer
Tray Dryer
Drum Dryer

Principle:

• Heated hollow metal drum rotates on its

longitudinal axis, which is partially dipped
in the solution to be dried.
• The solution is carried as a film on the
surface of the dryer and dried to form a
layer.
• A suitable knife scraps the dried
material, while the drum is rotating.
Drum Dryer
Drum Dryer
Spray Dryer
• Principle:
• Fluid to be dried is atomized into
fine droplets, which are thrown
radially into a moving stream of hot
gas.
• The temperature of the droplets is
immediately increased and fine
droplets get dried instantaneously
in the form of spherical particles.
• This process completes in a few
seconds before the droplets reach
the wall of the dryer.
Spray Dryer
Construction:
• Large cylindrical drying chamber, short
conical bottom.
• Inlet for hot air in the roof of the
chamber.
• Another inlet carrying spray-disk
atomizer is set in the roof.
• Spray disk atomizer is about 300
millimeters in diameter and rotates at
a speed of 3000 to 50,000 revolutions
per minute.
• Bottom of dryer is connected to a
cyclone separator.
Spray Dryer – • Drying of the material in spray dryer involves 3
working 1.
stages
Atomization of the liquid.
2. Drying of the liquid droplets
3. Recovery of the dried product
Atomization of the liquid to form liquid droplets:
• Feed is introduced through the atomizer either by
gravity or by using suitable pump to form fine
droplets.
• Properties of the final product depend on the
droplet form, hence, the selection of the type of
atomizer is important. Atomizer of any type:
pneumatic atomizer, pressure nozzle and spinning
disc atomizer may be used.
• Rate of feed is adjusted in such a way that the
droplets should be completely dried before
reaching the walls of the drying chamber. At the
same time, the product should not be over heated.
Spray Dryer – working
• Drying of the liquid droplets:
• Fine droplets are dried in the drying chamber by
supplying hot air through the inlet.
• Further, the liquid inside must escape by diffusing
through the shell at a particular rate.
• At the same time, heat transfer from outside to
inside takes place at a rate greater than liquid
diffusion rate.
• As a result, heat inside mounts up which allows the
liquid to evaporate at a faster rate.
• This tendency of a liquid leads to rise in the internal
pressure, which causes the droplets to swell.
• The shell’s thickness decreases whereas permeability
for vapour increases. If the shell is neither elastic
nor permeable, it ruptures and the internal pressure
escapes.
• The temperature of air is adjusted in such a way that
the droplets should be completely dried before
reaching the walls of the drying chamber.
 Spray Dryer – working

• Recovery of the dried product: centrifugal force of

atomizer drives the droplets to follow helical path. Particles
are dried during their journey and finally fall at the conical
bottom.
• All these processes are completed in a few seconds.
• Particle size of the final product ranges from 2 to 500 mm.
• Particle size depends on the solid content in the feed, liquid
viscosity, feed rate and disc speed.
• Spray dryers of maximum size have got evaporating capacity
up to 2000 kg per hour.
Spray Dryer
Spray Dryer
Vacuum dryer
Principle:
• In vacuum dryer, material is dried by using
vacuum.
• Due to application of vacuum the liquid boils
at a low temperature than the boiling point.
• So evaporation of liquid takes place faster
and at low temperature.
Vacuum dryer
Fluidized Bed Dryer

• Principle:
• Hot air (gas) is passed at high pressure
through a perforated bottom of the
container containing granules to be
dried.
• The granules are lifted from the bottom
and suspended in the stream of air.
• This condition is called fluidized state.
• The hot gas is surrounding every granule
to completely dry them.
• Thus, materials or granules are
uniformly dried.
Fluidized Bed Dryer - construction
 • Wet granules to be dried are placed in the detachable bowl.

Fluidized Bed • Bowl is pushed into the dryer.

• Fresh air is allowed to pass through air heaters.

Dryer – working • Hot air flows through bottom of bowl.

• Simultaneously fan is allowed to rotate.
• The air velocity is increased.
• When velocity of air is greater than settling velocity of granules,
the granules remain partially suspended in the gas stream.
• After some time, a point of pressure is reached at which
frictional drag on particles is equal to force of gravity.
• Granules rise in container because of high velocity ga and later
fall back in random boiling motion. This condition is known as
fluidized state.
• Gas surrounds every granule to completely dry them.
• Air leaves dryer by passing through the bag filter.
• Entrained particles remain adhered to the inside surface of the
bags. Periodically the bags are shaken to remove the entrained
particles.
• The residence time for drying is about 40 minutes. Material is
left for some time in the dryer for reaching ambient temperature.
• The bowl is taken out for discharging.
• The end product is free flowing.
Fluidized Bed Dryer – uses, advantages and
disadvantages
 Freeze dryer - Principle Freeze drying is also known as lyophilization, i.e.,
system is made solvent loving for removing the
same.

Principle:
• In freeze drying, water is removed from the
frozen state by sublimation, i.e., direct change
of water from solid into vapour without
conversion to a liquid phase.
• Solid-liquid-vapour equilibrium phase diagram of
water is useful to decide the experimental
conditions.
• The drying is achieved by subjecting the
Lyophilization, also known as freeze-drying or cryodesiccation, is a
material to temperature and pressures below
process that removes water from a material by freezing it and then the triple point and eutectic point.
lowering the pressure. The ice then sublimates, or turns directly from • Under these conditions, any heat transferred is
solid to vapor, without becoming a liquid.
used as latent heat and ice sublimes directly
Triple point: The condition of temperature and pressure under which into vapour state.
the gaseous, liquid, and solid forms of a substance change into each • The water vapour is removed from the system
other at equal rates so that the amount of each always remains the
same. by condensation in a cold trap maintained at a
Sensible heat is the heat that causes an object to change
temperature lower than the frozen material.
temperature. Latent heat is the heat the heat added to an object in
order for it to change state.
 Freeze drying
Freezing the material Conditions:
Temperature and pressures below the triple point
and eutectic point;
Reducing the pressure
Distance between subliming surface and condenser
must be less than the mean path of molecules. Because
Adding heat this increases the rate of drying

Temperature of condenser must be much lower than

Frozen water in the material changes the evaporated surface of frozen substance
directly to a vapor (sublimate).

Triple point: The condition of temperature and pressure under which the gaseous, liquid, and solid forms of
a substance change into each other at equal rates so that the amount of each always remains the same.

Eutectic point :The pressure and temperature at which the frozen solid vaporizes without conversion to a
liquid is referred to as the eutectic point. In freeze-drying, the eutectic point is the temperature at which
all the moisture in a material freezes into ice. During sublimation drying, the temperature of the material
should not be higher than its eutectic point, otherwise the material will melt, causing the material to boil,
causing bubbles, inflation or shrinkage inside the material, which will affect the quality of the freeze-dried
product.
Freeze dryer – construction
The construction of freeze dryer is made of four
basic components:

1.A Drying Chamber – Drying chamber in which trays

are loaded for vacuum drying.
2. Heat source- Heat supply in radiation source,
heating coils to provide latent heat of vaporization.
3. Vacuum Source- To remove air/oxygen vacuum
pump is used.
4. Vapour removal system- condensers, desiccants,
pumps or adsorption system.

A refrigerant is a chemical that absorbs heat and cools air

or objects in air conditioners and refrigeration systems.

An Isolation Valve is used in fluid management to stop the

flow of process fluids in a pipeline, this is usually for
maintenance or safety purposes.
 Freeze dryer – working
• Freeze drying is mainly used to remove the water from sensitive products, mostly of biological
origin, without damaging them, so they can be preserved easily, in a permanently storable
state and be reconstituted simply by adding water.
• Examples of freeze dried products are : antibiotics, bacteria, sera, vaccines, diagnostic
medications etc.
• Working involves:

Preparation and Pretreatment

Pre-freezing to solidify water

Primary drying

Secondary drying

Packing
 Why freeze drying in pharma ?

 Freeze-drying, also known as lyophilization, involves removing the moisture from the ampoules
by subjecting them to low temperatures and vacuum conditions. This process preserves the
integrity and stability of the drugs or substances inside the ampoules.

 Many pharmaceutical products lose their potency/viability in liquid state if dried in air at
normal atmospheric pressure. while some products may be heat sensitive or oxygen sensitive.
So to stabilize such type products, freeze drying is used for drying.
Example: Blood serum, plasma, antibiotics, hormones, bacterial cultures, vaccines etc.
 Pretreatment
Freeze dryer- working
1
•Pressure reduction: A vacuum pump lowers the pressure
inside the freeze-dryer.
 Solution is pre-concentrated – •Heat addition: Heat is added to the material to help the
water sublimate.
shortens drying ; product becomes
•Sublimation: The water sublimates from the surface of the
porous. material.
Pre-freezing •Condenser: A cold condenser provides a surface for the
2 water vapor to solidify on, and protects the vacuum pump
from the water vapor.
 To solidify water; frozen solid Primary drying stage removes easily removable moisture.
During this stage, about 98% to 99% water is removed.
 If not frozen solid, evaporation will occur and
Still traces of moisture is present in the sample.
the sample will not achieve the same
preservation properties that occur with
sublimation. 4 Secondary drying

3 Primary drying Removal of residual moisture under high vacuum.

Traces of moisture is removed. Temp is raised ;

 sublimation of ice under vacuum; a phase of the vacuum is lowered than in primary drying
freeze-drying process that removes water from a
frozen material through sublimation, Packing
5
 Conditions to be maintained (triple point & After vacuum is replaced by inert gas, the
eutectic point. bottles and vials are closed.
 Freeze dryer- working
• Pretreatment
• Prior to freezing
• Solution is pre-concentrated under normal vacuum tray drying.
• This reduces actual drying by 8 to 10 times. (shortens drying)
• The final product becomes more porous.
• Liquid or solid desiccants are also used for this purpose.
• Pre-freezing to solidify water
• Since freeze drying is a change in state from solid phase to gaseous phase, material
to be freeze dried must be adequately prefrozen.
• The method of freezing and the final temperature of the frozen product can affect
the ability to freeze dry the material.
• Vials, ampoules or bottles in which aqueous solution is packed are frozen in cold
shelves (about -50°C). During this stage, cabinet is maintained at low temperature
and atmospheric pressure.
• The normal cooling rate is about 1 to 3 Kelvin per minute so that large ice crystals
with relatively large holes are formed on sublimation of ice. This is also responsible
for giving a porous product.
 Freeze dryer - working
• Primary drying (sublimation of ice under vacuum)
• Material to be dried is spread as much large surface as possible for sublimation.
• Temperature and pressure should be below the triple point of water. i.e., 0.0098°C and 0.533 kilopascals (4.58 mmHg) for
the sublimation, when water alone is present.
• When a solution of solid is dried, the depression of freezing point of water occurs. Hence, it is essential that the
temperature be brought below the eutectic point. The pressure and temperature at which the frozen solid vaporizes
without conversion to a liquid is referred to as the eutectic point.
• Depending on the drug substance dissolved in water, the eutectic point is determined.
• The usual range is from -10°C to 30°C. The condition of 1 to 8 K below eutectic point is sufficient. Vacuum is applied to
the tune of about 3 mmHg (0.4 kilopascals) on the frozen sample. The temperature is linearly increased to about 30°C in a
span of 2 hours.
• Heat is supplied which transfers as latent heat and ice sublimes directly into vapour state. The heat controls the
movements of ice layer inwards. It has to be controlled in such a manner so as to get highest possible water vapour at ice
surface without melting the material. As soon as vapour molecules are formed, these are removed. The overall driving
force is the temperature and vapour pressure difference between evaporating surface and condenser.
• As the drying proceeds, thickness of the frozen layer decreases and the thickness of partially dried solids increases.
• Primary drying stage removes easily removable moisture.
• During this stage, about 98% to 99% water is removed.
• Still traces of moisture is present in the sample.
 Freeze dryer - working

• Secondary drying (removal of residual moisture under high vacuum)

During this stage, traces of moisture is removed.
The temperature of the solid is raised to as high as 50 to 60 ° C, but
vacuum is lowered below that is used in primary drying (50 mm Hg).
The rate of drying is very low and it takes about 10 to 20 hours.
• Packing:
After vacuum is replaced by inert gas, the bottles and vials are closed.

(An inert gas is a gas that is chemically inactive and doesn't react with many substances)
 Freeze dryer – uses, advantages and disadvantages
• Uses:
• In the production of dosage forms, such as injections, solutions and suspensions.
• Drying of – blood plasma, bacterial and viral cultures, human tissue, antibiotics, plant extracts. Steroids, vitamins, enzymes.
• Other food items (prawns, mushrooms, meat and poultry products), coffee and tea concentrates and citrus fruit juices are dried.
• Advantages:
• Thermolabile materials can be dried.
• Denaturation does not occur.
• Migration of salts and other solutes does not take place.
• Loss of volatile material is less.
• Moisture level can be kept as low as possible without decomposition.
• Sterility can be maintained.
• The final product can be stored at ambient temperature, if well sealed by providing inert atmosphere.
• Material can be dried in its final container such as single dose and multiple dose vials.
• Disadvantages:
• Economic cost is high.
• Difficult to adopt the method for solutions containing non-aqueous solvents.
• Period of drying is high (rarely less than 10 hours). Time cannot be shortened.
• Product is prone to oxidation, due to high porosity and large surface area. Therefore, the product should be packed in vacuum or
using inert gas or in a container impervious to gases.