BASICS OF DRY

1. DRYING
AN IMPORTANT UNIT OPERATION OF
PHARMACEUTICAL INDUSTRY
ABDUL MUHEEM
M.PHARMA 2ND YR
(PHARMACEUTICS)
JAMIA HMADRAD

2. CONTENT-
• Introduction
• Purposes
• Period of drying
• Classification of dryers
• Special types of dryers
• references

3. INTRODUCTION TO DRYING PROCESS
 Drying can be described by three processes
operating simultaneously:
1. Energy transfer from an external source to the water
or organic solvent
 Direct or Indirect Heat Transfer
2. Phase transformation of water/solvent from a liquid-
like state to a vapour state
 Mass Transfer (solid characteristics)
3. Transfer vapour generated away from the API and
out of the drying equipment

4.  Drying APIs is an important operation for the
production of consistent, stable, free-flowing
materials for formulation, packaging, storage and
transport
 Particle attrition or agglomeration can result in
major differences in particle size distribution
(PSD), compressibility and flow characteristics
 Equipment selection
 Drying specifications

5.  Purpose: To reduce the moisture level of wet granules
Why do it What are the What are the problems
equipment
To keep the residual Direct Heating Static Over drying (bone dry)
moisture low enough Solids Bed Dryers
(preferably as a range) to Excess fines
prevent product Direct Heating Moving
deterioration Solids Bed Dryers Possible fire hazard
Ensure free flowing Fluid Bed Dryer
properties
Indirect Conduction
Dryers

6. PERIODS OF DRYING
•Warm up period :A-B
•Constant Rate Period (B-C)
 HT dependent
•Falling rate period (C-D)
 MT dependent

8. DRYERS IN THE PHARMA INDUSTRY
 Dryers can be classified according to:
 Heat transferring methods
 Direct: Fluidised, Tray, Spray, Rotary Dryers, etc..
 Indirect: Cone, Tumble, Pan Dryers, etc…
 Continuous/ Batch processing
 Continuous: large quantities/small residence time
 Batch: small quantities/ long residence time

9. TRAY DRYERS
 a batch tray dryeR consists of a stack of
trays or several stacks of trays placed in a
large insulated chamber in which hot air is
circulated with appropriately designed fans
and guide vanes.

10.  It is possible to convert
the batch tray dryer into
a continuous unit. Figure
shows the so-called
Turbo dryer, which
consists of a stack of
coaxial circular trays
mounted on a single
vertical shaft. The
product layer fed onto
the first shelf is leveled
by a set of stationary
blades, which scratch a
series of grooves into
the layer surface. The
blades are staggered to
ensure mixing of the
material.

11. ROTARY DRYERS
 The cascading rotary
dryer is a continuously
operated direct contact
dryer consisting of a
slowly revolving
cylindrical shell that is
typically inclined to the
horizontal a few degrees
to aid the transportation
of the wet feedstock
which is introduced into
the drum at the upper
end and the dried
product withdrawn at the
lower end.

12.  VACCUM DRYERS
For drying of granular solids or slurries, vacuum
dryers of various mechanical designs are
available commercially. They are more
expensive than atmospheric pressure dryers
but are suited for heat-sensitive materials or
when solvent recovery is required

13. FLUID-BED DRYERS (FLUIDIZED-BED DRYERS
•Concept of fluidization
•Gas velocity realizing the change from
stationary(fixed) bed into fluidized bed is
called the critical fluidized velocity
ucritical.
•When gas velocity is increased to the
particle free setting velocity u0 , the
particle will be carried over, u0 is called the
carried over velocity ucarried.
ucritical<uoptimum<ucarried
7

14. •CHARACTERISTICS OF FLUID-BED to Dust Collector
DRYERS: ADVANTAGES:HIGH HEAT AND Feed
MASS TRANSFER RATES; SIMPLE Hot Air
to Dust Collector product
discharge
Distributo r Plate
STRUCTURES; LOW FABRICATING Feed to Dust Collector
Dry product disch arg e
COSTS; CONVENIENT MAINTENANCE; Hot Air Dust Feed
to Collector
to Dust Collector
Feed Hot Air
HIGHER THERMAL EFFICIENCY THAN Distributo r Plate
Feed Hot
Dry product Air Distributo r Plate
disch arg e
PNEUMATIC CONVEYING DRYERS; Hot AirDistributo r Plate
Dry product disc
DRYING TIME CAN BE CHANGED; Distributo r product disch arg e
Dry Plate
APPLIED TO DRYING OF GRANULAR Dry product disch arg e
Horizontally separately
MATERIALS. fluidized compartments
(Fig. 5-25) can get even
•DISADVANTAGES: STRICT OPERATION drying and relatively low
AND CONTROL REQUIREMENTS; flow resistance.
MULTI-SEPARATELY FLUIDIZED
COMPARTMENTS(PLUG FLOW
DRYERS) HAVE COMPLEX 8
STRUCTURES AND GREAT FLOW

15. Feed
(3)PNEUMATIC CONVEYING DRYERS Section
Feed First
First Section Second Section Feed
Feed First Section
Characteristics: Second Section Room for separating solids
1)Great
First Section Section
Second
contacting area between Room for separating solids
air Feed
Cleaned air
Feed Feed
and solids;Higher heat air Feed
Cleaned
SecondRoom for sep
Section
First Section First separatin
transfer and mass transfer Feed ExhaustSection Section
Exhaust air First
air
First Feed for Section
Room Cleaned air
rates; Short drying Second Section Exhaust Section
First Second
Cleaned Section air
air
First Section Section Section
Second Second Room for separatingforsolid
Second Section sepa
Room
time(0.5~2s).
Exhaust for separating
air
2)Stable operation and fine Second Room for separating solidsRoomCleaned air
Section Room for separating solids
Feed
product quality. Cleaned air Cleaned air air
Exhaust
RoomFirst Section
for separating solids
Cleaned Cleaned Exhaust air Exhaust air
air air
CleanedExhaust air
air
Second Section air
Exhaust
Exhaust air for separating solids
Room
3)Applying to thermally sensitive and air
Cleaned easily oxidized
materials.
Exhaust air
Defects: Materials easily broken; great flow resistance; high
drying duct. (about 30m)
5

16. FREEZE DRYER
 Highly heat-sensitive solids, such as some
certain biotechnological
materials, pharmaceuticals and foods with high
flavor content, may be freeze dried at a cost that
is at least one order-of-magnitude higher than
that of spray drying – itself not an inexpensive
drying operation. Here, drying occurs below the
triple point of the liquid by sublimation of the
frozen moisture into vapor, which is then
removed from the drying chamber by
mechanical vacuum pumps or steam jet
ejectors. Generally, freeze drying yields the
highest quality product of any dehydration
techniques

18. BASIC ISSUES FOR PHARMACEUTICAL FREEZE-
DRYING
 7.1.1 New Dosage forms of pharmaceutical drugs
 According to its development, pharmaceutical dosage
form can be divided into the following generations：
 The first generation : simple ointment, pill and powder for oral
administration and external use.
 The second generation: the tablets, injections, capsules and
aerosols made by mechanical and automatic machines.
 The third generation: slow-release or controlled-release dosage
forms that form a new drug delivery system (DDS) .
 The fourth generation:targeted dosage forms that form a targeted
drug delivery system.
 The fifth generation: the automatic release dosage forms inside the
body when the patients have a serious illness.
 At present, the third and fourth generations of dosage
forms are most concerned by scientists.

19.  In order to realize these new drug delivery
system, many new techniques are developed
in the formulation of dosage form, such as
 solid dispersion,
 inclusion,
 emulsion,
 liposomes,
 microencapsulation.

20. 7.1.3 BASIC PROCESS OF BIOLOGICAL DRUGS FREEZE-
DRYING
 The technical procedures of drug freeze-drying
consist of four processes:
 preparation and freezing,
 primary drying (sublimation drying),
 secondary drying (desorption drying)
 package.
 The temperature, vacuum for each process have to
be controlled precisely.
 The freeze-dried drugs are dry and porous solids.
 They can be stored in room temperature or in refrigerator
for a long time.

21.  1. Preparation and freezing of drugs
 In order to form a stable porous structure after freeze drying, the
concentration of drug solution must be a specific value.
 Excipients should be added into the low dose thermal sensitive
drugs (hormone, enzyme, vaccine) to reinforce the structure of
freeze-dried products.
 Lyoprotectant should be added into the biological protein-type drugs
or slow-release drugs with bio-membrane to protect proteins from
denaturation and the bio-membrane from damage.
 The end temperature of pre-freezing must be lower than the glass
transition temperature (Tg) or eutectic temperature (Te) of the drug
solution.

22.  2. Primary drying (sublimation drying)
 are performed at low temperature and vacuum.
 The drying progresses gradually from the surface to the
center of the products.
 The pores or channels formed by the sublimation ice
become the ways of vapor to escape.
 The boundary between drying layer and frozen layer is
known as the sublimation interface.
 The temperature of the sublimation interface is a critical
parameter to be controlled in primary drying process.
 90% water in drugs is removed after primary drying.
 In primary drying process, the temperature of frozen
layer must be lower than Te or Tg’.
 The temperature of dried layer must is lower than the
collapse temperature (Tc).
 The temperature of the heater in the drying chamber
should be controlled strictly.

23.  3. Secondary drying (desorption drying)
 purpose : to remove a portion of the bound water.
 The moisture content of drugs is lower than 3% after
secondary drying.
 Because of large absorption energy, the product
temperature in secondary drying must be
increased high enough to remove the bound water,
and on the other hand, this temperature cannot
induce denaturation of proteins and deterioration
of biological drugs.
 The Tg of the products increases gradually with the
decrement of water in secondary process.
 So the drying temperature of the products can be
increased gradually, but cannot be higher than Tg.

24.  4. Encapsulation process
 When the secondary drying process is complete,
plugging system in the chamber is used directly to
plug the vials in order to prevent the freeze dried
drugs from oxidation and water absorption.
 The encapsulation can also be completed after filling
nitrogen gas into the chamber.

25. 7.1.4 CHARACTERISTICS OF FREEZE-DRYING
TECHNOLOGY FOR DRUGS
 characteristics of freeze-drying technology
for drugs are
 can prevent the active components in from
denaturation or loss of biological activity.
 can protect the components in drugs from oxidation.
 can greatly reduce the loss of volatile components in
drugs.
 can inhibit the growth of microorganism and the
activity of enzyme in drugs.

26.  Freeze dried drugs will maintain the original structure.
 Freeze dried drugs have good rehydration property.
 Freeze dried drugs can be stored at room temperature
for a long time
 The initial cost of freeze-drying equipment is larger.
Freeze drying is a time and energy consuming process.
 It is very difficult to control the parameters at optimum
level.

27. 7.1.5 CRITICAL PROBLEMS OF FREEZE-DRYING IN
DRUGS
 1. Temperature Control and identification
of drying procedures
 Frozen drugs will melt, collapse or crimple if the temperature is
higher than the optimum temperature.
 if the temperature is too low, refrigeration load will causing
excessive energy consumption and the sublimation rate will be
decreased greatly

28.  2. Cooling Rate in freezing process
 freezing process determines the drying rate and
the quality of freeze-dried product.
 The optimum cooling rates vary with different
biological agents.For instance,
 slow freezing is usually beneficial to protein
polypeptide-type drugs.
 Fast freezing is usually beneficial to the virus and
vaccine.

29.  3. Types and concentration of
lyoprotectant
 The molecular structure of the active components is
different for different biological agents.
 The types and concentration of lyoprotectants
required in freeze drying are also different.
 Up to now, there is not a universal lyoprotectant
applied to all of the biological agents.

30. DRYER FOR SLURRY AND SUSPENSION
 SPRAY DRYER

32. DRUM DRYERS
 In drum dryers, slurries or pasty feedstocks are dried
on the surface of a slowly rotating steam-heated
drum. A thin film of the paste is applied on the surface
in various ways. The dried film is doctored off once it
is dry and collected as flakes (rather than powder).

33. BAND DRYER
 For relatively free-flowing granules and extrudates that
may undergo mechanical damage if they are dispersed,
band dryers are a good option. It is essentially a conveyor
dryer wherein the band is a perforated band over which
the bed of drying solids rests. Drying air at rather low
velocities flows upwards through the band to accomplish
drying.

34. TUNNEL DRYER
 In this simple dryer concept, cabinets, trucks or trolleys containing
the material to be dried are transported at an appropriate speed
through a long insulated chamber (or tunnel) while hot drying gas
is made to flow in concurrent, countercurrent, cross-flow or mixed
flow fashion. In the concurrent mode, the hottest and driest air
meets the wetted material and hence results in high initial drying
rates but with relatively low product temperature (wet-bulb
temperature if surface moisture is present).

35. MICROWAVE (MW) AND RADIO FREQUENCY (RF)
DRYING
 Unlike conduction, convection or radiation, dielectric
heating heats a material containing a polar compound
volumetrically, i.e., thermal energy supplied at the
surface does not have to be conducted into the
interior, as limited by Fourier's law of heatconduction.
This type of heating provides the following
advantages:
 · Enhanced diffusion of heat and mass
 · Development of internal pressure gradients which
enhance drying rates
 · Increased drying rates without increasing surface
temperatures
 · Better product quality

36. REFERENCES
 AULTON PHARMACEUTICS : THE DESIGN
AND MANUFACTURE OF MEDICINE
 CLASSIFICATION AND SELECTION OF
INDUSTRIAL DRYERS Arun S. Mujumdar
 DRYERS FOR PARTICULATE SOLIDS,
SLURRIES AND SHEET-FORM MATERIALS
Arun S. Mujumdar

37. Thanks