Pharmaceutical Unit Operations - DRYING

Assist. Prof. Özge İnal

PHA 3005-Pharmaceutical Technology- I
2020-2021 Fall Semester
 Definition of Drying

Many pharmaceutical operations, including those used to produce

active pharmaceutical ingredients and excipients, use water or
organic solvents as essential processing aids.

However, the continued presence of these processing aids may

harm manufacturing operations or the safety and stability of the
final pharmaceutical product.

Drying is a common unit operation used to reduce the levels of

water or organic solvent in pharmaceutical materials to
acceptable levels.
Drying process in pharmaceutical technology

 The granules to be pressed into tablets or filled into capsules

are dried
 Tablets, granules, particles are dried during coating processes
 Nanoparticles, microspheres and microcapsules are dried after
preparation
 Materials are dried to assist grinding process
 Freeze-drying (lyophilization) process
 Drying processes applied in the preparation of sterile injection
powders
Besides,

 Obtaining plant-derived medicines, the plants must be dried

prior to extraction, the resulting extracts should be dried

 Purification and drying of inorganic salts (sodium chloride,

calcium carbonate etc.)

 To obtain dry powder form of drugs and excipients

Mechanisms of Heat Transfer
Humidity is measured by:

 Gravimetric method:
Air is passed over a certain substance of known weight, which can
absorb moisture, such as phosphorus pentoxide. The absolute
humidity of the air is calculated from the change in the weight of
the substance
 Mechanical Hygrometers:
Contains a spring or composite bar that expands
or contracts depending on the ambient humidity.
 Electronical Hygrometers

 Psychrometers
Psychrometer

A psychrometer is a pair of identically shaped

thermometers, one of which is covered with a wet
sleeve. It measures humidity by taking both a
wet-bulb and a dry-bulb temperature reading.

With those two values known, the other properties of the air, including
its moisture content, can be determined by computation or by reading
a psychrometric chart.
Humidity ratio

Dry bulb temperature

Introduction to Drying Process

Drying can be described by three processes operating simultaneously:

 The first process is energy transfer from an external source to the

water or organic solvent in the material.
 The second process is the phase transformation of the water or
organic solvent from a liquid or liquid-like state to a vapor state.
 The third process is the transfer of the vapor generated away from
the pharmaceutical material and out of the drying equipment.
Periods of Drying

• Warm up period (A-B)

• Constant Rate Period (B-C)
• Falling rate period (C-D)
First phase heating up
 Heat is transferred to the product.
 Product is heating up from the inlet condition to the
process condition. The rate of evaporation increases
dramatically during this period with mostly free
moisture being removed.
Second phase constant rate period
 Free moisture persists on the surfaces and the rate of evaporation alters very little as
the moisture content reduces. During this period drying rates are high, and higher inlet
air temperatures than in subsequent drying stages.
Third phase falling rate period
 This is the phase during which migration of moisture from the inner side of each particle
to the outer surface becomes the limiting factor that reduces the drying rate.

The point C, where the drying rate begins to decrease, is called "critical moisture
content".
Drying Methods

The following points should be considered when

selecting the drying method to be applied to the
material to be dried:
1) Drying properties of the material
2) Properties of dry matter obtained
3) Properties related to drying process
4) Operating conditions
 Classification of dryers
I. Drying of solids with moisture
*Stationary (Static) bed dryers
a) batch types of static bed dryers
b) Continuous types of static bed dryers
*Moving bed dryers: vacuum dryers
*Fluid bed dryers

II. Drying of liquids in solution, suspension and slurry

*Pneumatic systems
*Freeze drying
According to heat transfer mechanism:

1- Direct dryers:
Heat reaches the material to be dried by hot air via convection.

2- Indirect Dryers:
Heat is transmitted by conduction. Heat reaches the material to be
dried by the container wall on which they are placed. Therefore
the material is in contact with the hot surface.

3- Dryers with IR radiation:

Drying occurs by absorption of IR light. Microwave dryers are in
this class.
I. Drying of solids with moisture

1- Stationary (Static) bed dryers:  There is no movement between the

 Tray Dryers particles of the material to be dried.
 Tunnel Dryers  The drying air or heated trays are in
 Microwave Dryers contact with the surface.

2-Moving bed dryers:  The particles are in motion

 Rotary Dryers by gravity or mechanical stirring.
 Rotating Tray Turbo Dryers  Heat and mass transfer is faster than
 Vacuum dryers system 1.

3-Fluid bed dryers

 Particles are suspended in an air stream or gas stream.

 That is to say a solid mixture in gas, similar to a boiling liquid.

 There is a faster drying than system 1 and 2.

 Tray Dryers Tunnel Dryers Microwave Dryers

 It operates by  They make the trays  By applying microwave

passing hot air mobile. The material energy to pharmaceutical
over the surface to be dried are fed systems to be dried,
of a wet solid that from one end in the dielectric materials such
is spread over air heated tunnel for as water and solvents
trays arranged in drying and collected with dissolved salts
racks. from the other end. absorb the energy
 Tray dryers are  The source of thereby increasing
the simplest and heating can be of molecular vibration.
least-expensive 1) Hot air circulation  They can be;
dryer type. 2) Infrared - stand-alone cabinets,
3) Microwave or - fluid bed,
4) Radio frequency. - vibrational capabilities,
- combination dryers with
vacuum
 Rotary Dryers Rotating Tray Turbo Dryers

 The cascading rotary dryer is a  Consists of a stack of

continuously operated direct slowly rotating circular trays.
contact dryer.  Material is fed onto the top tray.
 It consists a slowly revolving  After one revolution the material is
cylindrical shell that is typically wiped onto the next lower tray.
inclined to the horizontal a few
 Here it is mixed, leveled, and then
degrees to aid the transportation
after one revolution, is wiped to the
of the wet feedstock which is
next tray where the operation is
introduced into the drum at the
repeated.
upper end and the dried product
withdrawn at the lower end.
 Vacuum Dryers

 The total pressure surrounding the pharmaceutical material is reduced to

levels below the saturation pressure of the solvent at the interface
between the wet and dry layers causing generation of vapor.
 Vacuum can be supplied by conventional pumps, blowers, or steam jets.
 Heating fluid circulates through a jacket and enters and exits through
dynamic seals along the axis of rotation.
 With suitable vacuum levels, drying can be cost-effective at relatively low
product temperatures.
 Vacuum drying is particularly advantageous for heat- or oxygen-sensitive
products, for reducing the risk of dust explosions, and for applications
requiring solvent recovery or extremely low residual solvent levels
 Fluid Bed Systems

 Fluid bed-drying is a widely used Fluid bed dryers

example of the direct heating
classification.
Top Spray
 Drying is accomplished by
suspending the particles to be dried
directly in a stream of heated air or
other gaseous media.
 The intimate contact and high surface
areas available for transfer result in
fast, efficient drying, often making
fluid bed the approach of choice for
high-volume products
Bottom Spray
(Wurster coating) Tangential Spray
(Rotor pellet coating)
 Spray dryers

• Spray drying is a technique to generate powders by transforming the feed from

a liquid state into a dry form, by spraying the feed into a hot drying medium.
• The feed can be a solution, suspension, dispersion, or emulsion.
• The spray drying process mainly consists of five steps:
Concentration: Before introduced to the spray dryer, feedstock is usually
concentrated.
Atomization: Favors evaporation to a dry powder, by having optimum properties.
Droplet-Air Contact: In the chamber, atomized liquid contacts with hot gas, leading
to evaporation of a majority of the water or solvent contained in the droplets
within a few seconds.
Droplet Drying:Water or solvent evaporation takes places.
Separation: Cyclones, bag filters, and electrostatic precipitators may be used for
the final separation stage
ADVANTAGES

• rapid,
• continuous,
• reproducible
• single-step
• suitable for scaling without major modifications
• the possibility to dry a broad spectrum of compounds including
heat-sensitive substances without major detrimental effects
• Can be used to encapsulate drugs, extracts, aromatic oils,
pigments, and flavors within different types of carriers such as
polymeric nanoparticles (NPs) and microparticles.
Freeze drying (lyophilization)

A typical production scale freeze

dryer consists of:
A drying process employed to convert
solutions of labile materials into solids of - Refrigeration System
sufficient stability for distribution and storage - Vacuum System
- Control System
-the removal of ice or other frozen solvents - Product Chamber or Manifold
from a material through the process of - Condenser
sublimation and the removal of bound water
molecules through the process of desorption.

Sublimation is the transition of a substance

from the solid phase directly to the gas
phase without passing through an
intermediate liquid phase.
triple point

defined as the point at

which
-solid,
-gas,
-liquid
coexist as three separate
phases.

Lyophilization is carried
out below the triple point
to enable conversion of ice
into vapor, without entering
the liquid phase
Sublimation in the freeze drying process can be described as:

1. FREEZE - The product is completely frozen, usually in a vial, flask or

tray.

1.VACUUM - The product is then placed under a deep vacuum, well

below the triple point of water.

3. DRY – Heat energy is then added to the product causing the ice to
sublime.
1. PRIMER DRYING
2. SECONDER DRYING
Application areas

 preparation of sterile powders for injection,

 To obtain the peptide-protein active substances as dry raw materials,
 Blood products, biological materials, bacterial strains, vaccines and
sera are dosed in special containers and stored in lyophilized form
under aseptic conditions,

 Some special drug forms and

drug delivery systems are prepared
 Widely applied in the production of fruit and coffee extracts.
 Advantages of lyophilization Disadvantages of lyophilization

 Ease of processing a liquid,  Increased handling and

which simplifies aseptic handling processing time
 Enhanced stability of a dry  Need for sterile diluent
powder upon reconstitution
 Removal of water without  Cost and complexity of
excessive heating of the product equipment
 Enhanced product stability in a
dry state
 Rapid and easy dissolution of
reconstituted product