Drying

By
Dr. Hasan Muti

1
 Definition

• Is the removal of a liquid from a material by the

application of heat, and is accomplished by the
transfer of a liquid from a surface into an
unsaturated vapor phase.
• This definition applies to the removal of a small
amount of water from moisture-bearing table salt as
well as to the recovery of salt from the sea by
evaporation. Drying and evaporation are
distinguishable by quantities of liquid removed.

2
 Introduction

• There is no pharmaceutical plant engaged in the manufacture of tablets or

capsules or dry suspensions that does not contain dryers.
• Unfortunately drying is very important in the manufacturing point of view
to have a good distribution and compressibility of tablets.
• Drying of powders affects the stability of thermal labile products. So the
selection of drying temperature is very important.
• Any deterioration of the product (e.g., by microbial infection, oxidation,
thermal decomposition, contamination by metallic particles or by
unremoved organic solvent) must be avoided at any cost.
• In Light of that performed in inert gas to avoid oxidation or explosion if
solvent is flammable. To avoid thermal decomposition in many instances
vacuum and freeze drying must be employed.

3
 Introduction
•It is important that the residual moisture is
rendered low enough to prevent product
deterioration during storage and ensure free-flowing
and compactability properties during use.
•Residual solvents have to be removed also from the
powder, because it might affect the stability of
product and health of the users.
•Comfortable humidity is close to 50%( +/_ 10%)

4
 Moisture content of wet solids
•The moisture content of a wet solid is expressed as kg of moisture
associated with 1 kg of the moisture-free or “bone-dry” solid.
•Thus a moisture content of 0.4 means that 0.4 kg of water is
present per kg of the “bone-dry” solid that will remain after
complete drying.
•It will sometimes be calculated as percentage moisture content;
thus this example would be quoted as 40% moisture content
•Thus humidity refers to presence of water vapor (is the content of
water in the air) and moisture refers to presence water in liquid
form.
•Moisture is associated with the water content in liquid phase
present in any substance. ... Generally speaking, humidity is mainly
used to talk about the moisture (amount of water) in the air.

5
 Unbound water (loose water)
•Associated with a wet solid exists as a liquid and it
exerts its full vapor pressure.
•The pressure exerted by this gas phase in equilibrium
with its solid or liquid counterpart is known as vapor
pressure. ... For example, the amount of water vapor
will increase and the pressure will increase if a bottle of
water is heated up
•It can be removed readily by evaporation during drying
process and the resulting solid will not be completely
free from water molecules as it remains contact with
atmospheric air.

6
 Relative Humidity RH
•Is a simple solution of water in a mixture of gases.
•At a given temperature air is capable of “taking up” water vapor until it is
saturated (at 100% RH).
•Relative humidities can be quantified in term of percentage RH.
•Vapor pressure of water vapor in the air\vapor pressure of water vapor in
air saturated at same temperature X100.
•This is approximately equal to % saturation which is: Mass of water vapor
present per kg of dry air\Mass of water vapor required to saturate 1 kg of
dry air at the same temperature X100
•In simpler terms water activity (aw) is a measure of relative humidity (RH)

7
Loss of water

8
 Nonthermal methods
1. Expression. The squeezing of a wetted mass.
2. Extraction. The extraction of liquid from a solid by use of
solvent.
3. Adsorption. The adsorption of water from a solvent by the
use of desiccant such as anhydrous calcium chloride. (is
the adhesion of atoms, ions, or molecules from a gas, liquid,
or dissolved solid to a surface such as charcoal)
4. Absorption. The absorption of moisture from gases by
passage through sulfuric acid column. (Absorption is defined
as the process when one thing becomes part of another
thing, or the process of something)
5. Desiccation. Desiccation of moisture from solid using silica
gel in bottles.
9
Difference between adsorption and absorption

10
 Purpose of drying

1. Used as a process in the preparation of granules.

2. Processing of materials, e.g., preparation of dried
aluminum hydroxide, spray drying of lactose.
3. To reduce bulk and weight , thereby lowering the
cost of transportation and storage.
4. Aiding in the preservation of animal and
vegetable drugs.
5. To reduce the chemical reactivity with water.

11
 Behavior of Solids During Drying

• How would one know if 8 or 12 hours are required to dry a

batch weight of material in a certain dryer?
• How can one determine the size of a particular type of
dryer required for drying a substance from one moisture
level to the desired moisture content?
• The rate of drying of a sample can be determined by
suspending the wet material on a balance in a drying
cabinet and measuring the weight of the sample as it
dries as a function of time

12
 Rate of Drying

• The difference in moisture content between any two

measurements divided by the time period between
measurements represents the rate of drying for this
time period.
• When a wet solid is first placed in a drying oven, it
begins to absorb heat and increases in temperature.
At the same time, the moisture begins evaporating
and thus tends to cool the drying solid.

13
 Classification of Solids Based on Drying Behavior

• Solids may be classified into two major categories on

the basis of their drying behavior namely:
1. Granular or crystalline type solids.
2. Amorphous solids.
• The water in crystalline solids is held in shallow and
open surface pores as well as in interstitial spaces
between particles that are easily accessible to the
surface.

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 Classification of Solids Based on Drying Behavior

• In the second category the moisture is an integral part of the

molecular structure as well as being physically entrapped in
fine capillaries and small interior pores.
• Typical pharmaceuticals of the first category are calcium
sulfate, zinc oxide, and magnesium oxide.
• Materials that fall into the second category are starch, casein,
yeast, insulin.
• All amorphous solids are more difficult to dry than granular or
crystalline solids.

15
Classification of Solids Based on Drying Behavior

• The moisture in crystalline solids is lost with little

hindrance by either gravitational or capillary
forces.
• The constant rate period is the major portion of
the drying curve, and this period continues until
the material has virtually no free water.
• Materials in this category are usually inorganic
and consequently are not affected by heat, unless
the temperature is high enough to change any
hydrate forms.

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Classification of Solids Based on Drying Behavior

• The moisture movement is slow in substances in

the second category.
• The liquid diffuses through structural obstacles
caused by the molecular configuration.
• The drying curves of these amorphous materials
have short constant-rate periods, ending at high
critical moisture contents.

17
 Equilibrium Moisture Content

• The moisture content of a material that is in

equilibrium with an atmosphere of a given relativity
of the material at this humidity.
• It is the moisture content at which the material exerts
a water vapor pressure equal to the vapor pressure of
the atmospheric surrounding it; thus it has no driving
force for mass transfer.
• EMC values of various materials may differ greatly
under the same conditions, despite the fact that they
are in equilibrium with their environment

18
 Equilibrium Relative Humidity

• The relative humidity surrounding a material at

which the material neither gains nor loses
moisture.
• At a given temperature , the ERH for a material is
determined by its moisture content, just as the
EMC is determined by the surrounding relative
humidity.

19
 Water Activity

• The water activity of a material is the ratio of the

water vapor pressure exerted by the material to
the vapor pressure of pure water at the same
temperature.
• The water activity value has special significance
because it is a measure of the relative chemical
activity of the water in the material.
• The smaller the water activity is, the smaller are
the chemical potential of the water and the
driving force for chemical reactions involving
water.
20
 Water Activity

• The most important effects of lowered water activity

are increased chemical stability and reduced
potential for micro-organism growth.
• Each microorganism has a critical (aw) below 0.86,
are tolerant and usually no growth occurs at or
below 0.62
• Water activity can be reduced by the addition of
solutes such as sucrose, glycerin, polyols, surfactants,
as well as by reduced moisture content.

21
 Bound water
•Part of the moisture content in a wet solid may be
adsorbed on surfaces of the solid or be absorbed
within its structure to such an extent that it is
prevented from developing its full vapor pressure
and from being easily removed by evaporation
•It is more difficult to remove than unbound water
•It is absorbed and attached to the surface of the
solid as individual water molecules which may form a
mono- (or bi) layer on the solid surface
•Bound water is the water that remains unfrozen at
temperature below 0°C usually – 20 °C
•Regarding the forms of water, bound water is
inversely related to water activity

22
 Bound Water
• As the % of bound water in food and drugs increases the water activity
decrease
• Water activity (aw) is calculate as the ration of the water vapor pressure of
the substance divided by the vapor pressure of the pure water at same
temperature.

• aw=p/p 0. where
aw = water activity, p= vapor pressure of water in drug
and p0 = vapor pressure of water at the same temperature

• RH(%) = 100X a w
• The ERH Equilibrium Relative Humidity is defined as the relative humidity of the air
surrounding the drug at which the product neither gains nor loses its natural
moisture and is in equilibrium with the environment .

aw= ERH/100
23
 Measurement Methods

• The equilibrium moisture content of a material can

be determined by exposing samples in a series of
closed chambers, such as desiccators, which are
partially filled with solutions that can maintain fixed
relative humidities in the enclosed air space.
• The exposure is continued until the material comes
to constant weight.
• The process, which can take more than a month for
some materials, can be accelerated.

24
 Psychrometry

• Psychrometry is the science of studying the various

thermodynamic properties of moist air and the use
of these properties to analyze conditions and its
effect on various materials and human being.
• Studying Psychrometry helps understanding different
constituents of air and how they affect each other,
which in turn discover (illustrates)various mysteries
of the atmosphere and the nature
• To make the air usable for drying purposes , its
temperature must be raised.
25
 Psychrometry
• Is the determination of the vapor concentration and carrying
capacity of the gas .
• A critical factor in drying operations is the vapor-carrying
capacity of the air, nitrogen, or other gas stream passing over
the drying material.
• The carrying capacity determines not only the rate of drying
but also the extent of drying, I.e., the lowest moisture content
to which a given material can be dried.
• The concentration of water vapor in a gas is called humidity of
the gas.
• The dew point is defined as the temperature to which a given
mixture of air and water vapor must be cooled to become
saturated .
26
 Theory of Drying
• Drying involves both heat and mass transfer
operations.
• Heat must be transferred to the material to be
dried in order to supply the latent heat required
for vaporization of the moisture.
• Mass transfer is involved in the diffusion of water
through the material to the evaporating surface,
in the subsequent evaporation of the water from
the surface, and in diffusion of the resultant vapor
into the passing air stream.

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 Theory of Drying

• The rate of evaporation of the film of liquid is related

to the rate of heat transfer .
• The rate of drying may be accelerated by:
1. Increasing the rate flow.
2. Raising the inlet air temperature.
3. Speeding the rate of radiation.
4. Reducing the thickness of materials .
5. Increasing the air velocity.

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 Theory of Drying
6. Dehumidifying the inlet air, thus increasing
the humidity differential.
7. Application of a microwave or dielectric
field. Heat is generated internally by the
interaction of the applied electromagnetic
field with the solvent.
• When the surface becomes partially or
completely dry, the heat and mass transfer
equations become more complex. In this case the
rate of drying is controlled by the rate of diffusion
of moisture from the interior of the material.
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 Theory of Drying

• The process becomes further complicated when

the drying surface causes a shrinkage of the solid.
• This phenomenon can cause blocking and
distortion of the capillary structure and thus
interfere with the transfer of internal water to the
surface of the material.
• Case hardening phenomenon, in which the
surface of the solid becomes harder than the
interior and less permeable to the transmission of
interior moisture.
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 Drying of Solids - Loss on Drying

• The moisture in a solid can be expressed on a wet-

weight or dry-weight basis.
• On a wet-weight basis , the water content of material
is calculated as a percentage of the weight of the wet
solid, whereas on the dry weight basis, the water is
expressed as a percentage of the weight of the dry
solid.
• % LOD = Wt. Of water in sample X 100
Wt. Of dry sample

31
 Drying of Solids - Moisture Content

• Another measurement of the moisture in a wet solid

is that calculated on a dry-weight basis.
• % MC= wt. Of water in sample x 100
wt. Of dry sample
• If exactly 5 g of moist solid is brought to a constant
dry weight of 3 g:
– MC = 5-3\3 x 100 = 66.7%
– LOD = 5-3\3 x 100 = 66.7%

32
 Types of drying methods
•When considering how to dry a material,
the following points should be considered:
1.Heat sensitivity of materials
2.Physical characteristics of material, e.g.
melting point and shape.
3.Nature of liquid to be removed
4.Scale of the operation
5.Necessity for asepsis
6.Available source of heat (steam, electrical)
33
 Efficient drying
The general principles for efficient drying can
be summarized as:
1.Large surface area for heat transfer
2.Efficient heat transfer per unit area
3.Efficient mass transfer of evaporated water
through any surrounding boundary layers
4.Efficient vapour removal

34
 Dryers in the pharmaceutical
industry
•Number and variety of dryers have been
reduced recently for standardization and
globalization of manufacturing

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 Dynamic convective dryer
Fluidized-bed dryer
•An excellent method of obtaining good contact
between the warm drying air and wet particles.
•The air will pass through the bed of solids from
below and great turbulence and particle mixing
with good contact between air and particles, the
turbulence conditions lead to high heat and mass
transfer rates, the fluidized-bed technique therefore
offering a mean of rapid drying

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Fluid-bed dryer

37
 Advantages of Bed Dryer
1. High drying rate, so drying time is short
2. Drying comes from all individual particle at same
time and rate
3. Temperature is uniform and controlled precisely
4. More spherical particles due to attrition
5. The free movement of individual particle reduces
the risk of soluble materials migrating during
drying
6. Keeping granules separate and reduce aggregation
7. Simple handling where bed can be moved easily

38
 Disadvantages of bed-dryer
1. Turbulence may cause excessive attrition and
damage of some granules and formation of
dust
2. Fine particles may become entrained in the
fluidizing air and must be collected by bag
filters
3. Vigorous movement may generate static
charges
4. A mixture of lactose and starch can explode if
ignited by sparking caused by static charges
39
 Conductive drying
Vacuum oven
•In vacuum dryer, material is dried by the application of
vacuum. when pressure is lowered, the water boils at low
temperature. Hence the evaporation is faster.
•This equipment is a good example of a conduction dryer
though it is not used extensively
•Operating pressure can be as low as 0.03-0.06 bar, at which
water boils at 25-35 °C
•Vacuum oven is that drying takes place at a low
temperature and since there is little air present, there is
minimum risk of oxidation
•Rarely used nowadays in production area
•It is used mainly in the laboratories for LOD
40
Vacuum oven

41
 Use of radiation
Microwave dryer
•Microwave radiation in the wavelength of 10 mm to 1 m
has been found efficient heating and drying method
•Microwaves are produced by an electronic device known
as a magnetron.
•If polar solvent molecules are present the
electromagnetic field induce orientation of the dipole in
the molecules
•As the field oscillates, the polar molecules oscillate with
the filed, resulting in increased kinetic energy from dipolar
molecules and their collision with others.
•This manifested (obvious or apparent) in thermal or heat
energy
42
 Use of radiation
Microwave dryer
The rate of heating is proportional to the
dielectric constant of materials placed in
the field.
Water has dielectric constant 70 and the
granules around 10, then the water will be
heated more rapidly than other
components in the granules
Energy saving of 70 % compared to fluid
bed drying
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Advantages of microwave drying
•It provides rapid drying at fairly low temperatures.
•The thermal efficiency is high since the dryer casing and
the air remain cool.
•Most of the microwave energy is absorbed by the liquid in
the wet materials
•The bed is stationary avoiding problems of dust and
attrition
•Solute migration is reduced as there is uniform heating of
wet mass
•Equipment is highly efficient and refined
•Granulation end point is possible by measuring the residual
microwave energy within the dryer
44
 Disadvantages of microwave drying
•The batch size of commercial production is small
Care must be taken to shield operators form
microwave radiation. It might damage eyes and
testes and causes physiological abnormalities.
The physical and electrical properties of each
material determines how quickly and evenly it will
dry in the microwave, but microwaves generally
penetrate to a depth of 1 to 1.5 inches, so thin layer
of powders is needed for successful drying

45
Microwave dryer

46
 Spray dryer
•It differs from most other dryers in that
they can handle only fluid materials such as
solutions, slurries and thin pastes.
•The fluid is dispersed as fine droplets into a
moving stream of hot gas, where they
evaporate rapidly before reaching the wall
of the drying chamber.

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 Spray dryer
•The product dries into a fine powder,
which is carried by the gas current and
gravity flow into collection system
•It 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 an individual
solid particle
48
 Spray dryer
•When the liquid droplets come into
contact with the hot gas, they quickly reach
a temperature slightly above the wet-bulb
temperature of the gas
•The surface liquid is quickly evaporated,
and a tough shell of solid may form in its
place.

49
Spray Dryer

50
 Major use
•Can be used to dry heat sensitive materials
•Changing the physical form of material for
used in tablets and capsules
•Encapsulation of solid and liquid particles
•Used to dry oxidative materials
•E.g. as commonly used material is spray
dried lactose and cefuroxime axetil
•Extremely used in coating or encapsulation

51
Advantages of the spray-drying process
1. Millions of small droplets which give a large
surface area for heat and mass transfer, so the
evaporation is very rapid
2. The droplets do not attain a high temperature
3. Efficient packing with high density
4. Free flowing product
5. Increase the dissolution rate
6. Labor cost is very low
7. It can be used as a continuous process if
required
52
Disadvantages of the spry-drying process
•The equipment is very bulky and is very
expensive
•The thermal efficiency is rather low
since the air must still be hot enough
when it leaves the dryer to avoid
condensation of moisture

53
Formation of product in spray drying

54
 Freeze drying
•Is a process used to dry extremely heat sensitive
materials. E.g. proteins, blood products and even
microorganisms and antibiotics
•The initial liquid solution or suspension is frozen,
the pressure above the frozen state is reduced and
the water removed by sublimation and leaving the
dry product in place
•The water passes directly from the solid state (ice)
to the vapor state without passing through the
liquid state.
Triple point is: a temperature and pressure at which the phases gas, liquid and solid of
the substance coexist in thermodynamic equilibrium
55
Phase diagram with freeze drying process

56
Application of the phase diagram of water to freeze
drying

1. Freezing the solution

2. Reducing the atmospheric pressure above
the ice to below that of the triple point of
the product
3. Adding heat to the system to raise the
temperature to the sublimation curve to
provide the latent heat of sublimation

57
 Advantages of freeze drying
1. Drying takes place at very low temperature, so
decomposition is minimized
2. The solution is frozen such that the final dry
product is a network of solid occupying the
same volume as the original solution (product is
light and porous)
3. The porous form of the product gives ready
solubility of the freeze dried product
4. There is no concentration of the solution prior
to drying
5. Little contact of air and oxidation is minimized

58
 Disadvantages of freeze drying
1. The porosity, ready solution and
complete dryness of the product result in
one with a very hygroscopic nature.
Unless dried in the final container and
sealed in situ.
2. The process is very slow and uses
complicated plant that is very expensive
3. It is limited to valuable and unstable
products
59
 Uses of freeze drying
•This method is used for those product which
could not be dried by any other heat methods.
•E.g. antibiotics, blood products, vaccines such
as BCG, yellow fever, smallpox, enzyme
preparations such as (hyaluronidase) and
microbiological cultures.
•The latter enables specific microbiological
species and strains to be stored for long periods
with viability of about 10% on reconstitution

60
 Solute migration during drying
•Solute migration is the phenomenon that can occur during
drying (movement of solution within a wet system).
•The solvent moves towards the surface of a solid (from
where it evaporates), taking any dissolved solute with it.
•Many drugs and binding agents are soluble in granulating
fluid and during the drying of granulates these solutes can
move forwards the surface of the drying bed or granule and
be deposited there when the solvent evaporates.
•Migration is two types, (intergranular and intergranular)

61
 Conclusion

•The different drying equipments are

available now, but the suitable dryer is
selected based on:
1. Materials,
2.Cost
3.Availability of heating resources
4.Nature of the product intended to be
manufactured 62