HEAT TRANSFER

0531-2103
FALL 2024
CONTENTS
• Definition
• Methods of Heat transfer
• Evaporation
• Distillation
• Drying
• Freeze drying
DEFINITION
• Heat transfer refers to the actual flow of heat energy
between two objects. This energy flows from a system at
higher temperature to a system at lower temperature.
• Difference in temperature is a must.
• Most of the pharmaceutical processes such as distillation,
evaporation, drying, sterilization, extraction of volatile oils
are the example of heat transfer.
 METHODS OF HEAT TRANSFER

• Transfer of heat
from one system
to another can
take place by three
methods and all
three can occur
simultaneously.
 CONDUCTION
• Conduction is a specific mode of
heat transfer in which this energy
exchange takes place in solids or
fluids with no convective motions
from the region of high
temperature to the region of lower
temperature due to the presence of
temperature gradient.
CONDUCTION - EXAMPLE
 CONVECTION
• Convection is the process of heat transfer by the bulk movement
of molecules within fluids such as gases and liquids. The initial
heat transfer between the object and the fluid takes place
through conduction, but the bulk heat transfer happens due to
the motion of the fluid.
• Convection is the process of heat transfer in fluids by the actual
motion of matter.
• It happens in liquids and gases.
• It may be natural or forced.
CONVECTION
Formula:

Where
h= heat transfer coefficient
A= surface area
CONVECTION - EXAMPLE
RADIATION
• During radiation the transfer of heat energy from the source
of heat to the object takes place through space by means of
electromagnetic waves, which travel in straight lines at the
speed of light.
• Energy is transmitted through space to a receiving object
where it is absorbed and manifested as heat.
RADIATION – EXAMPLE
EVAPORATION
• Evaporation means the free escape of vapors from the
surface of a liquid below its boiling point.
• It is a slow process and a surface phenomenon. When the
attractive forces of surface decreases, then evaporation
occurs. It can occur at any temperature.
• So evaporation maybe defined as the removal of liquid from
a solution by boiling the solution in a suitable vessel from
where the vapors are easily withdrawn and a concentrated
residue is left behind.
FACTORS AFFECTING EVAPORATION
• Temperature
Evaporation is directly proportional to temperature. But during
evaporation, temperature that will cause the least possible
decomposition must be used.
• Duration of exposure
Exposure to a higher temperature for a short period of time
maybe less destructive for active substances than a lower
temperature for a longer period of time.
FACTORS AFFECTING EVAPORATION
• Moisture content
Some drug constituents decompose more rapidly in the presence of
moisture especially at a raised temperature. This is understandable
since many breakdown reactions are hydrolysis.
• Concentration
With the loss of liquid, increasing solid proportions result in elevation
of boiling point of solution. This also leads to rise in viscosity. Both
these factors increase the risk of damage to thermolabile
constituents. These problems maybe minimized by ensuring
turbulent flow conditions.
DISTILLATION

• Distillation is a process of separating the constituents of a

mixture by vaporizing the liquid and passing the vapors
through a cold surface thereby condensing the vapor to
obtain liquid.
• This process involves a change in state from liquid to vapor
and again to liquid.
• Distillation is the combination of evaporation and
condensation.
DISTILLATION
SIMPLE DISTILLATION
• This procedure is conducted using simple apparatus comprised
of boiler and a condenser.
• Simple evaporators like rotary evaporators can e used.
• The process can be carried out under reduced temperature as
low as possible.
SIMPLE DISTILLATION
SIMPLE DISTILLATION
• Advantage • Disadvantage
• It is simple, cheap, easy and • The final product may contain
economic method. impurities.
• It requires less energy. • Azeotropic mixtures cannot be
separated by simple distillation.
• This process requires single
run and thus is comparatively • Not suitable for mixtures
faster. containing thermolabile
components.
• The volume of mixture should be
not more than 2/3rd of the
container.
APPLICATION
• Simple distillation is primarily used for the production of distilled water.
• Many volatile oils are separated by simple distillation.
• It is also used in the separation of organic solvents from mixtures.
• It is used to separate non-volatile components from volatile ones.
• It is used in preparing pharmaceutical spirits.
FRACTIONAL DISTILLATION

• The theory of fractional distillation for separating

miscible liquids shows that the process depends
upon heating the mixture, repeatedly condensing the
vapor and re-heating the liquid and thus altering the
equilibrium between liquid and vapor.
• This process can be carried out by fractionating
column.
FRACTIONAL DISTILLATION
FRACTIONAL DISTILLATION
• Advantages • Disadvantages
• Frictional distillation gives good • Fractional distillation cannot be used to
solvent recovery separate miscible liquids, which form
pure azeotropic mixtures.
• Fractional distillation is easy to
use and operate. • It is expensive because it requires large
• Fractional distillation is also structures, heavy-duty materials, and
specialized machinery.
highly efficient, especially for
systems that use stacked • It also requires staff to be fully trained.
distillation columns, which • It presents a wide range of risks for the
produce more output at lower
costs. people who are involved in it. For
example, explosion.
• It helps to produce much- • It can contribute to environmental
needed fuel. pollution.
APPLICATION
• Fractional distillation is used for the separation of miscible liquids
such as acetone and water, chloroform and benzene.
• Fractional distillation is suitable for a system when the boiling point of
the mixture is always intermediate between those of pure
components.
• There is neither a maximum nor a minimum in the composition
curves (azeotropic mixtures). Examples include benzene and toluene,
carbon tetrachloride and cyclohexane, and water and methanol.
DRYING
• Drying is a process in which water or another solvent is removed by
evaporation from a solid, semi-solid, or liquid. Drying is often a final
step in the production or packaging of pharmaceutical products.
• The drying process involves a source of heat and a facility to remove
the produced vapors. In the majority of pharmaceutical intermediates
or finished products the solvent removed is water.
• The effectiveness of drying processes has a large impact on product
quality and process efficiency. For example, in the batch processing of
pharmaceuticals drying is a key manufacturing step.
DRYING-APPLICATIONS
1. Drying is used to remove excess moisture or other volatiles from coatings and various
substrates.
2. It is used to reduce and control moisture levels in solid materials in the manufacture of
many materials.
3. It is most important in the processing of highly thermolabile products which are not
stable in liquid form. The lyophilization enables longer shelf life of thermolabile
materials and make them suitable for storage and transport of the product. For example,
drying of biological products such as blood plasma, vaccines, enzymes,
microbiological cultures, hormones and antibiotics
4. Drying is used to make the material easy or more suitable for handling and processing. In
the manufacturing of bulk drugs or for large-scale production of synthetic drugs, drying
is essential to get free-flowing materials. For example, dried aluminum hydroxide, spray-
dried lactose, etc.
DRYING-APPLICATIONS
5. It has applications in avoiding or eliminating moisture that initiates corrosion and
decreases the product or drug stability. For example, to avoid deterioration or
contamination of crude drugs of animal and vegetable origin, synthetic and semi-
synthetic drugs.
6. It is used to maintain and improve good properties such as flowability,
compressibility etc. of a materials. For example, drying fresh plants such as
belladonna leaves, nux vomica before subjecting them to size reduction.
7. It is used in the production of tablets and granules to improve tablet properties
especially, compression of viscous and sticky material.
8. Drying is used to improve solubility of materials by modifying their physical form.
For example, milk and coffee extract is dried to convert them into instant soluble
power form.
DRYING-APPLICATIONS
9. Drying is necessary to make material light in weight that help to reduce the cost of
transportation of large volume materials (liquids).
10. Drying is used as the final step in evaporation, filtration, and crystallization and to
preserve materials from environmental factors.
11. Drying is used to maintain and improve shelf life of thermolabile and hydrolytic
substances for longer period of time. It is necessary to avoid deterioration of blood
products, skin and tissue that undergo microbial decomposition.
12. Drying significantly decreases rate of chemical reactions as well as chances of
microbial attack or enzymatic actions and thus improves stability.
DRYER
There are various types of Dryer used in Pharmaceutical Industries
• Fluid Bed Dryer
• Tray Dryer
• Belt Dryer
• Vacuum Tray Dryer
• Spray Dryer
• Rotary Dryer
NON THERMAL DRYING
• Expression of a solid to remove liquid e.g. squeezing of sponge to
remove liquid.
• Extraction of liquid from a solid using a solvent.
• Adsorption of water from a solvent by the use of desiccants
• Absorption of moisture from gases by passage through a sulfuric acid
column
• Desiccation of moisture from a solid by placing it in a sealed
container with a moisture removing material (silica gel)
PRINCIPLE OF DRYING
• Heat Transfer
Heat must be transferred to the material to be dried in order to supply the
latent heat required for vaporization of the moisture. The driving force of
this transfer is temperature differential.

• Mass Transfer
Mass transfer is involved in the diffusion of water through the material to
the evaporating surface and in diffusion of the resultant vapor into the
passing air stream. The driving force of moisture diffusion is humidity
differential. This diffusion is greatly influenced by the molecular and
capillary structure of the solid.
DETERMINATION OF MOISTURE
• The moisture in a solid can be expressed on two basis-
• Wet-weight basis
• Dry-weight basis

• On a wet-weight basis, the water content of a 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.
DETERMINATION OF MOISTURE
• Loss on drying (LOD)
• In pharmacy, it is an expression of moisture content on a wet-weight
basis, which is calculated using following equation

• Moisture content (MC)

• It is a way of measurement of the moisture in a wet solid on a dry-weight
basis, which is calculated using following equation
FREEZE DRYING
• Many products of pharmaceutical interest
lose their viability in the liquid state and
readily deteriorate if dried in air at normal
atmospheric pressures. These products
may be heat sensitive or they may react
with oxygen.

• In order to keep the products stable, they

must be dehydrated to a solid state.

• For these reasons, freeze drying is used

 FREEZE DRYING-PRINCIPLE
The main principle involved in
freeze-drying is a phenomenon
called sublimation, where water
passes directly from a solid-state
(ice) to the vapor state without
passing through the liquid state.
Sublimation of water can take place
at pressures and temperatures
below the triple point of water
(4.579 mm of Hg and 0.0099 ºC).
FREEZE DRYING-PRINCIPLE
The material to be dried is first
frozen and then subjected under a
high vacuum to heat (by conduction
or radiation or by both) so that
frozen liquid sublime, leaving only
non-volatile solid, dried components
of the original liquid. The
concentration gradient of water
vapor between the drying front and
condenser is the driving force for the
removal of water during freeze
drying.
FREEZE DRYING-PROCESS
1. Pretreatment: In this stage product is treated for freeze concentration,
solution-phase concentration, preserve product appearance, stabilize
reactive products, increase surface area, and decrease high vapor pressure
solvents concentration prior to freezing. In many instances, the decision to
pre-treat a product is based on theoretical knowledge of freeze-drying and
its requirements or is demanded by cycle time or product quality
considerations.

2. Freezing: During the freezing stage, the liquid sample is cooled down to −
40 to − 60 °C until pure crystalline ice forms from part of the liquid and the
remainder of the sample is freeze-concentrated into a glassy state where
the viscosity is too high to allow further crystallization.
FREEZE DRYING-PROCESS
3. Primary drying: In primary drying the ice formed during the freezing is
removed by sublimation under vacuum at low temperatures, leaving a
highly porous structure in the remaining amorphous solute that is
typically 10% water. This step is carried out at pressures of 10−4 to 10−5
atmospheres, and a product temperature of – 45 to – 20 °C. The
sublimation during primary drying is the result of coupled heat- and mass-
transfer processes.
4. Secondary drying: This is last step wherein most of the remaining water
is desorbed from the glass as the temperature of the sample is gradually
increased upto 10 – 15 °C while maintaining low pressures. Ideally, the
final product is a dry, easily reconstituted cake with a high surface area
and low moisture content (below 5% w/w).
FREEZE DRYING
• Advantages • Disadvantages
• Oxidizable substances are well • Removing volatile compounds may
protected under vacuum conditions. require a high vacuum.
• Long drying period owing to 95%- • Most expensive unit operation.
99.5% water removal.
• Stability problems such as low-
• Loaded quantities are accurate and have temperature stress are associated with
content uniformity. individual drugs.
• Little contamination owing to the • There are some issues associated with
aseptic process. sterilization and sterility assurance of
the dryer chamber and aseptic loading
• Minimal loss in volatile chemicals and of vials into the chamber.
heat-sensitive nutrient and fragrant
components.
• Constituents of the dried material
remain homogeneously dispersed.
APPLICATIONS OF FREEZE DRYER
1. Pharmaceutical companies often use freeze-drying to increase the shelf life of
products, such as vaccines and other injectables.
2. By removing the water from the material and sealing the material in a vial under a
vacuum, the material can be easily stored, shipped, and later reconstituted to its
original form for injection.
3. Freeze-drying is used to preserve biologicals and make it very lightweight.
4. It is used to preserve blood products in freeze-dried form.
5. It is used in the chemical synthesis where products are often freeze-dried to make
them more stable, or easier to dissolve in water for subsequent use.
6. As freeze-drying can effectively remove solvents that can be used in bio-separations as
a late-stage of the purification procedure.
7. In addition, it is capable of concentrating substances with low molecular weights that
are too small to be removed by a filtration membrane.