Drying of Pharmaceutics

1. 1
Drying
Prepared by
Mr. Sahebro S. Boraste

2. DRYING
 Drying is defined as the removal of small amounts
of water or other liquid from a material by the
application of heat.
or
 Drying is defined as the removal of all or most of
the liquid by supplying heat to cause thermal
vapourization.
Drying VS Evaporation
Drying Evaporation
Final product is dry solid Final product is conc. Solution or
suspension or wet slurry
Vapour is removed at temperature
below its boiling point
Water is removed at its boiling point

3. APPLICATIONS OF DRYING
 Preparation of bulk drugs : In the preparation of bulk drugs
drying is the final stage of processing. A few examples are:
dried aluminium hydroxide, spray dried lactose, powdered
extracts.
 Preservation of drug products : Drying is necessary in
order to avoid deterioration. A few examples are:
—
Drug product Decomposition type
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

4.  Improved characteristics : Drying produces
materials of spherical shape, uniform size, free flowing
and enhanced solubility.
Some specific areas of importance are:
(1) Granules are dried to improve the fluidity and
compression characteristics.
(2) Viscous and sticky materials are not free flowing.
Drying modifies these characteristics.
 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.

5. TERMS IN DRYING
In wet solid 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
the same temperature.
 Unbound water (moisture) is the amount of water
(moisture) held by the material that exerts an equ
ilibrium vapour pressure equal to that of pure water at
the same temperature.

6. MECHANISM OF DRYING PROCESS
• Into the dryer, warm air stream is introduced to provide
the latent heat.
• This. heat is taken up by the material and the moisture
evaporates.
Drying is a three step process:
1. Heat transfer takes place from the heating medium to
the solid material.
2. Mass transfer involves the transfer of moisture to the
surface of .solids and subsequently vapourisation from
the surface in to surrounding.
3. Transfer of relased vapour away from pharmaceutical
material and out of drying equipment.

7. THEORIES OF DRYING MECHANISM
Diffusion theory
 Diffusion theory the rate of flow of water iis proportional
to moisture gradient.
 According to this theory, moisture movement may be as
follows.
1. Water diffuses through the solid to the surface and
subsequently evaporates into the surroundings.
2. Evaporation of water occurs at an intermediate zone,
much below the solid surface, then vapours diffuse
through the solid into air.

8. Capillarity theory
 Capillarity theory is applicable to porous granu-
lar solids with network of inter-connected pores and
channels.
 As the drying starts, a meniscus is formed in the capillary
and exerts a force.
 This is the driving force for the movement of water
through pores towards the surface.
 The capillary force is greater in small pores Compared to
the large pores. Therefore, small pores pull more water
from the larger pores and thus large pores get emptied
first.
 This theory is applicable to hygroscopic material.

9. Pressure gradient theory
 Pressure gradient theory is applicable to drying of solids
by the application of radiation.
 The radiation generates internal heat interacts with the
polarized molecules and ions of the material.
 This field aligns the molecules in order, which are
otherwise randomly oriented.
 When the field is reversed, the molecules return to the
original orientation giving up kinetic energy( heat) inside
the solid surface and liquid is vaporised.

10. 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.
 Equilibrium moisture content in a wet mass is shown
below.
 The temperature and humidity of air kept constant so
the solid may absorb of loose moisture

11.  When air ( of constant temp. & humidity) is continuously
passed over soild containing moisture more than EMC,
the solid looses water continuously till EMC is reached.
This phenomenon is called desorption.
 When air ( of constant temp. & humidity) is continuously
passed over soild containing moisture less than EMC, the
solid absorbs water continuously till EMC is reached. This
phenomenon is called sorption.

12. MEASUREMENT OF EMC
Procedure:
1. The solid samples are placed in a series of closed
chambers such as desiccators.
2. Each chamber consists of solution (desiccant), where
samples are exposed to different humidity conditions.
3. The exposure is continued until the material attains a
constant weight
4. The difference in the final and initial weights gives the
moisture content.
5. The moisture content is measured twice; before keep
ing the material into the storage bin and while taking
out the material.

13.  During storage, the material may lose/gain moisture.
(hygroscopic) gaining or loosing (efflorescent).
 Equilibrium moisture curve is drawn by taking relative
humidity (%) on x-axis and moisture content on y-axis

14. APPLICATIONS OF EMC
1. The EMC curve permits the selection of experimental
conditions to be used for drying the product.
2. Drying should be stopped when the moisture content
reaches the level of the EMC .
3. Over drying can be avoided, because overdried product
quickly regains the moisture from the ambient conditions.
4. If the moisture content is to be reduced, the relative
humidity of the ambient air must be reduced as a first
step.
 This can be done mechanically on a large scale using an
air-conditioning system.
 On scale dessiccators can be used.

15. FACTORS AFFECTING EMC
 Nature of material:
1. Nonporous insoluble solids have an EMC of practically
zero. e.g. talc and zinc oxide.
2. For fibrous or colloidal organic substances, the EMC
values are high and variable.
For example, cotton fabric has high EMC (10
to 15 %) under normal atmospheric conditions.
3. For porous solids, the EMC values are much higher and
variable. The water may be held in fine capillaries that
have no access to the surface.
 Nature of air:
1. For air of zero humidity, EMC of all materials is zero.
2. As the temperature of air increases, the EMC of solid
decreases

16. TERMS IN DRYING
 Free moisture content:
It is amount of water that is free to evaporate from solid
surface.
Free moisture content = total water content – EMC
 % loss on drying (LOD) =
mass of water in sample X 100
total mass of wet sample
 % Moisture content =
mass of water in sample X 100
mass of dry sample

17. DRYING RATE
 Drying rate =
weight of water in sample
Time (Hrs) X weight of dry solid
 Drying rate is plotted against the midpoints of the time
period.
 Drying rate curve is obtained by plotting FMC on x-axis
and drying rate on y-axis..

19. 1. Initial Adjustment Period
 The time corresponding to AB represents the initial
adjustment period.
 During this period, the solids absorb heat and the
temperature increases & the moisture begins to
evaporate and thus tends to cool the drying solid.
 After some time, the temperature stabilizes (heating
and cooling rates become equal).
 This temperature is equal to the wet bulb temperature
of the drying air and is referred by the point B.

20. • A’B’ represents a drying period when the sample is taken from
reactor at high temperature to a dryer at a low temperature

21. 2. Constant rate period
 The time corresponding to BC represents the constant
rate period .
 The temperature remains constant and rate of drying is
constant.
 The moisture evaporating from the surface is replaced by
the water diffusing fromthe interior of the solid.
 The rate of diffusion is equal to the rate of evaporation.
 At this stage the temperature is similar to wet bulb
temperature.
 When all other variables are kept constant, the constant
drying rate is in_dependent of the material being dried.

22.  As the water is freely remove, particle size of the solids
influences the drying rate.
 The moisture content at the end of constant rate (point C)
is referred to as the critical moisture content (CMG).
 Critical moisture content is a point below which the
movement of moisture from the interior is no longer
sufficient to saturate the surface.
 For any material, critical moisture content decreases with
decreasing the particle size

23. 3. First falling period
1. The time corresponding to CD represents the first
falling rate period
2. During this period, the surface water is no longer
replaced at a rate fast enough to maintain a continuous
film on the surface.
3. Dry spots begin to appear and the rate of drying
begins to fall off.
4. For first-falling rate period, the temperature of the solid
surface is above the wet-bulb temperature. The point D
is referred to as the second critical point.

24.  At this point, the film of surface water is completely
evaporated

25. 4. Second falling period
 The time corresponding to DE represents the second
jailing rale period.
 During this period, the rate of drying falls even more
rapidlY than the first falling rate.
 During this period, the rate of drying is dependent on the
rate of diffusion of vapour of moisture to the surface of the
solid.
 During the period, the surface temperature approaches
the temperature of dry air. Point
 E is referred to as equilibrium moisture content.

26.  Beyond E, the drying rate is equal to zero. Hence
temperature and moisture content remain constant.
 Beyond Point E continued srying is waste of time &
energy.

27. TRAY DRIER
 Principle
 Hot air is continuously circulated. Forced convection
heating takes place to remove moisture from the solids
spread in trays.
 Construction:
1. It consists of a rectangular chamber whose walls are
insulated.
2. Trays are placed inside the heating chamber. The
number of trays may vary with the size of the dryer.
3. laboratory size driers may contain three trays, dryers of
industry size may contain more than 20 trays.

28. 4. Each tray is rectangular or square and about 1.2 to 2.4
m2 in area.
5. Trays are usually loaded from 10.0 to 100.0 millimetres
deep.
6. The distance between the bottom of upper tray and
(upper) surface of the substance loaded in the
subsequent tray must be 40.0 mm.

29. Working:
1. Wet solid is loaded into trays. Trays are placed in the
chamber.
2. Fresh air is introduced through inlet, which passes
through the heaters and gets heated up.
3. The hot air is circulated by means of fans at 2 to 5 m/s.
4. The water is picked up by air. As water evaporates from
the surface, the water diffuses from the interior of the
solid by capillary action.
5. Moist air is discharged through outlet.
6. Thus constant temperature and uniform airflow over the
material can be maintained for achieving uniform drying.

30.  Uses
1. Sticky materials, plastic substances,. granular mass or crystalline
materials, precipitates and pastes ,Crude drugs, chemicals,
powders, granules can be dried.
 Advantages:
1. handling of materials (loading and unloading) can be done
without losses.
2. (2) Tray dryer is operated batch-wise.
(a) Each batch of material can be handled as a separate entity.
(b) The batch sizes in the pharmaceutical industry are relatively
small (250 kg or less per batch) compared with the chemical
industry (1000 kg or more per hour).
(c) The same equipment is readily adjusted for use in drying a
wide variety of materials.
(d) Valuable products can be handled efficiently.
3. Temperature can be adjusted to meet the conditions of
thermosen-sitve materials.

31.  Disadvantages:
1. Require time and labour to load and unload.
2. Time consuming process.
3. Dusty solids cannot be dried.
Video links:
1. https://www.youtube.com/watch?v=fmrvZ1F9x40
2. https://www.youtube.com/watch?v=TNtObZiI8uo

32. DRUM DRIER
 Principle :
 In drum dryer, a 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, on account of steam
heated drum.
 A suitable knife scraps the dried material, while the drum
is rotating.
 Mechanism is simple evaporation.

33.  Construction:
1. It consist of hollow steel drum horizontally mounted made up of steel
of 0.6 – 3 .0 diameter and 0.6 – 4.0 length whose external surface is
smoothly polished.
2. Below the drum, feed pan is placed in such a way that the drum dips
partially in to the feed.
3. On one side of the drum a spreader is placed and on the other knife
is placed to scrap the dried material.
4. A storage bin (or a conveyor) is placed connecting the knife to collect
the material in the storage bin.

34. Working:
1. Steam is passed inside the drum whose heat transfer
coefficient is high.
2. Drying capacity is directly proportional to the surface area
of the drum.
3. Heat is transferred by conduction to the material.
4. Simultaneously drum is rotated at a rate of 1-10 revolutions
per minute.
5. The liquid material present in the feed pan adheres as a
thin layer to the external surface of the drum during its
rotation.
6. The material is completely dried during its journey in
slightly less than one rotation
7. The dried material is scrapped by the doctor's knife, which
then falls into a storage bin.
8. The time of contact of the material with hot metal is 6 to 15
seconds only.

35.  Parameters controlled in drum dryer
 Speed of drum drier
 Temperature of the feed
 Film thickness
 Steam temp. of the drum
 Uses
: used for drying solutions, slurries, suspensions, etc. The
products dried are milk products, starch products, ferrous
salts, suspensions of zinc oxide, suspension of kaolin, yeast,
pigments, malt ex tracts, antibiotics, glandular extracts,
insecticides, DDT, calcium and barium carbonates.

36.  Advantages:
1. In drum dryer, drying time is less, only a few seconds.
Therefore heat sensitive materials can be dried.
2. (Drum dryer occupies less space, as it is compact when
compared to spray dryer.
3. As a thin film of liquid is formed on the large heating
surface, mass transfer are high. & rates of heat transfer
4. The product obtained is completely dried and is in the final
form.
5. It is used for continuous drying/processing.

37. Disadvantages:
1. The initial purchase cost and the maintenance cost of
drum dryer are higher than spray dryer.
2. Maintenance cost of a drum dryer is higher than spray
dryer.
3. Skilled operators are essential to control feed rate, film
thickness, speed of rotation and temperature.
4. it is not suitable for solutions of salts with less solubility.
5. The heat treatment is higher than in spray drying. The
solid product is less attractive.
Videos:
1. https://www.youtube.com/watch?v=msGOevNYVL4
2. https://www.youtube.com/watch?v=yuxEarAGfwM

38. SPRAY DYER
 Principle :
1. In spray dryer, the fluid to be dried is atomized into fine
droplets, on to a moving stream of hot gas.
2. The heating medium (hot air) is in contact with the
material .
3. The temperature of the droplets is immediately increased
and fine droplets get dried instantaneously in the form of
spherical particles.
4. Drying takes place by simple evaporation rather than
boiling.
5. This process completes in a few seconds before the
droplets reach the wall of the dryer

39.  Construction :
1. It consists of a large cylindrical drying chamber with a
short conical bottom, made up of stainless steel
2. An inlet for hot air is placed in the roof of the chamber.
3. Another inlet carrying spray-disk atomizer is set which is
about 300 m in diameter and rotates at a speed of 3,000
to 50,000 revolutions per minute. Bottom of the dryer is
connected to a cyclone separator.

40. Working :
Drying of the material in spray dryer involves 3 stages.
(1) Atomization of the liquid.
(2) Mixing of droplets.
(3) Drying of the liquid droplets.
(4) Recovery of the dried product

41. Atomization of the liquid to form liquid droplets :
1. The feed is introduced through the atomizer by using
suitable pump to form fine droplets.
2. The properties of the final product depend on the droplet.
3. Atomizer of any type; pneumatic atomizer, pressure nozzle
and spinning disc atomizer may be used.
4. The rate of feed is adjusted in such a way that the droplets
should be completely dried before reaching the walls of the
drying chamber. At thee same time, the product should not
be over heated.

42. Drying of the liquid droplets :
1. Fine droplets are dried in the drying chamber by
supplying hot air through the inlet.
2. The surface of the liquid drop is dried immediately to
form a tough shell.
3. The liquid inside must escape by diffusing through the
shell at a particular rate.
4. At the same time, heat transfer from outside to inside
takes place at a rate greater than liquid diffusion rate
which allows the liquid to evaporate at a faster rate.
5. The temp. of air should be such that droplets should be
completely dried before reaching drying chamber.

43. Recovery of dried product
1. Centrifugal force of atomizer drives the droplets to follow
helical path.
2. Particles are dried during their journey and finally fall at the
conical bottom.
3. All these processes are completed in a few seconds.
4. Particle size of the final product ranges from 2 to 500 µm.
5. Particle size depends on solid content in the feed, liquid
viscosity, feed rate and disc speed.

44. Uses :
 Spray dryers are used compulsorily when
(1) the product is a better form than that obtained by any other
dryer.
(2) the quantity of the material to be dried is large, and
(3) the product is thermolabile, hygroscopic or undergoes
chemical decomposition.
 Few products dried by spray dryer are: acacia, citric acid,
hormones,soaps, adrenaline, coffee extract,
detergents,milk,sulphur, blood extracts,vaccines.

45.  Advantages:
1. continuous process and drying is very rapid which
completes within 3 to 30 seconds.
2. Labour costs are low.
3. Free flowing product of uniform spheres
4. Fine droplets provide large surface area for heat and
mass transfer.
5. Product shows excellent solubility.
6. Either the solution or suspension or thin paste can be dried
in one step to get the final product ready for package.
7. It is suitable for the drying of sterile products.
8. Reconstituted product appears more or less similar to the
fresh material.

46. Disadvantages:
 Bulky equipment with high cost.
 Such a huge equipment is not always easy to operate.
 The thermal efficiency is low, as much heat is lost in the
discharged gases.
Related videos:
1. https://www.youtube.com/watch?v=6Jj4RkvgH0c
2. https://www.youtube.com/watch?v=BwxOYVdpneU
3. https://www.youtube.com/watch?v=sK1UbVveBK8

47. FLUIDIZED BED DRYER
Principle :
1. In fluidised bed dryer, hot air (gas) is passed at high
pressure through a perforated bottom of the container
containing granules to be dried.
2. The granules are lifted from the bottom and suspended
in the stream of air.
3. This condition is called fluidized state.
4. The hot gas is surrounding every granule to completely
dry them. Thus, materials or granules are uniformly dried

48. Construction:
1. Bed dryers are available as vertical fluid bed dryer and
horizontal fluid bed dryer.
2. The dryer is made up of stainless steel.
3. A perforated detachable bowl is placed at the bottom of
the dryer, which is used for placing and removal of
material.
.

49. 4. fan is mounted in the upper part for circulating hot air.
5. Fresh air inlet, prefilter and heat exchanger are connected
serially to heat the air to the required temperatures.
6. Bag filters are placed above the drying bowl for the
recovery of fines
Working
1. The wet granules to be dried are placed in the detachable
bowl .
2. The bowl is pushed into the dryer.
3. Fresh air is allowed to pass through a prefilter, which
subsequently gets heated by passing through a heat
exchanger.
4. The hot air flows through the bottom of the bowl.
Simultaneously fan iis allowed to rotate.
5. The air velocity is gradually increased.

50. 6. When the velocity of the air is greater than settling velocity of
granules, the granules remain partially suspended in the gas
stream.
7. The granules rise in the container because of high velocity
gas (1.5 to 7.5 metres per minute) and later fall back in a
random boiling motion. This condition is said to befluidised
state.
8. The gas surrounds every granule to completely dry them.
9. The air leaves the dryer by passing through the bag filter.
10. The entrained particles remain adhered to the inside
surface of the bags are which is shako remove the entrained
particles.

51. Uses :
Fluidised bed dryer is popularly used for drying of granules
in the production of tablets.
Advantages:
1. requires less time for complete drying, compared to tray
dryer.
2. available in different sizes with the drying capacity
3. drying containers are mobile, making handling simple
and reducing labour costs
4. thermal efficiency is 2 to 6 times than tray dryer.
5. mixing efficiency is also high.
6. Hot spots are not observed in the dryer,
7. Used for thermolabile products.
8. can be used either as batch type or continuous type

52.  Disadvantages :
 Many organic powders develop electrostatic charges' during
drying.
 To avoid this, efficient electrical earthing of the dryer is
essential.
 Fine particles may become en trained and must be
collected by bag filters
Related videos:
1. https://www.youtube.com/watch?v=vz4audqdx5o
2. https://www.youtube.com/watch?v=6288nnB7UFE
3. https://www.youtube.com/watch?v=9GN2R8nglWc&t=17s

53. FREEZE DRYER/ LYOPHILIZATION
 Principle :
1. 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.
2. The drying is achieved by subjecting the material to
temperature and pressures below the triple point.
3. Under these conditions, any heat transferred is used as
latent heat and ice sublimes directly into vapour state.
4. The water vapour is removed from the system by
condensation in a cold trap maintained at a temperature
lower than the frozen material.

54. Construction :
 It consists of
1. Drying camber in which trays are loaded.
2. Heat supply in the form of radiation source, heating coils.
3. Vapour condensing or adsorption system.
4. Vacuum pump or steam ejector or both.
 The chamber for vacuum drying is generally designed for
batch operation.
 It consists of shelves for keeping the material.
 The distance between subliming surface and condenser
must be less than the mean path of molecules, which
increases the rate of drying.

55.  The condenser consists of a relatively large surface cooled
by solid carbon dioxide slurred with acetone or ethanol.
 The temperature of the condenser must be much lower than
the evaporating surface of frozen substance

56. Working :
 The working of freeze dryer consists of the following steps.
1. Preparation and pretreatment
2. Prefreezing to solidify water
3. primary drying (sublimation of ice under vacuum)
4. secondary drying (removal of residual moisture under high
vacuum)
5. Packing

57. Preparation and pre-treatment :
1. The volume of solution introduced the container is limited
by its capacity.
2. Satisfactory freeze drying beyond a certain limit of depth of
liquid is not possible
3. Therefore pre-treatment is eseential.
4. The solution is pre-concentrated under normal vacuum.
5. This reduces the actual drying by 8 to10 times.
6. The final product becomes more porous.

58. Pre-freezing to solidity water
 Vials, ampoules or bottles in which the aqueous solution is
packed are frozen in cold shelves (about —50 0C).
 During this stage, cabinet is maintained at low temperature
and atmospheric pressure.
 The normal cooling rate is about 1 to 3 K/min so that large
crystals with relatively large holes are formed on sublimation
of ice.
 This also responsible for giving a porous product.

59. Primary Drying
(sublimation of ice under vacuum)
1. Material is spread in large surface for sublimation.
2. The temp. & pressure should be below triple point of water
0.0098 0C & 0.533 kPa (4.58 mmHg).
3. The temp. & pressure at which the frozen solid vaporizes
with out conversion to liquid is called eutectic point.
4. Heat is supplied as latent heat and ice sublime to vapour.
5. During this stage 98-99 % moisture is removed.

60. Secondary drying
(Removal of moisture under high vacuum)
1. During this stage traces of moisture is removed.
2. The temp. of solid is raised as 50-60 0C, but pressue is
lowered.
3. The rate of drying is very low and takes about 10-20 hrs.
Packing: after vacuum is replaced by inert gas, the bottles
& Vials are closed.
Uses: commonly used in production of injection, solution
and suspensions.
Used for drying blood plasma, bacterial & Viral cultures,
human tissue, antibiotics, plant extracts, steroids,
vitamins and enzymes.

61. Advantages.
1. Thermolabile material can be dried.
2. The product retains its bulk volume. It is porous and uniform.
3. The reconstitution of the material is easy.
4. Denaturation does not occur.
5. Loss of volatile material is less.
6. Moisture level can be kept as low as possible without
decomposition.
7. Material can be dried in its final container such as single
dose an multiple dose vials.
8. Sterility can be maintained.

62. Disadvantages:
1. Product prone to oxidation due to porosity and large surface
area. So product packed in vacuum.
2. Equipment and running cost is high.
3. Difficult for solution with non-aqueous solvents.
4. Time for drying is high.
Related videos:
https://www.youtube.com/watch?v=eE993Vs7j8s
https://www.youtube.com/watch?v=gHOi_ioUPTc