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DRYING

AN IMPORTANT UNIT OPERATION OF PHARMACEUTICAL


INDUSTRY

ABDUL MUHEEM
M.PHARMA 2ND YR
(PHARMACEUTICS)
JAMIA HMADRAD
CONTENT-

Introduction

Purposes

Period of drying

Classification of dryers

Special types of dryers

references
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
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
Purpose: To reduce the moisture level of wet granules

What are the What are the Why do it


problems equipment

Over drying (bone dry) Direct Heating Static To keep the residual
Solids Bed Dryers moisture low enough
Excess fines (preferably as a range) to
Direct Heating Moving prevent product
Possible fire hazard Solids Bed Dryers deterioration
Fluid Bed Dryer Ensure free flowing
Indirect Conduction properties
Dryers
PERIODS OF DRYING

Warm
Warm up
up period
period :A-B
:A-B
Constant
Constant Rate
Rate Period
Period (B-
(B-
C)
C)
HT
HT dependent
dependent
Falling
Falling rate
rate period
period (C-D)
(C-D)
MT
MT dependent
dependent
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
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.
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.
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.
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
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

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CHARACTERISTICS OF FLUID-BED
to Dust Collect or
Feed
Hot Air
Dist ribut o r Plat e
Dry pro du ct disch arg e

DRYERS: ADVANTAGES:HIGH HEAT


AND MASS TRANSFER RATES; SIMPLE product

STRUCTURES; LOW FABRICATING to Dust Collector


Feed
Hot Air
discharg
e

COSTS; CONVENIENT MAINTENANCE;


Distributo r Plate
Dry product disch arg e

HIGHER THERMAL EFFICIENCY THAN


PNEUMATIC CONVEYING DRYERS;
to Dust Collector
Feed
Hot Air
Dist ributo r Plate
Dry product disch arg e

DRYING TIME CAN BE CHANGED;


to Dust Collect or to Dust Collector
Feed Feed
Hot Air
Hot Air
Dist ribut o r Plat e
Distributo r Plate
Dry product disch arg e
Dry product disch arg e

APPLIED TO DRYING OF GRANULAR


MATERIALS. Horizontally separately
DISADVANTAGES: STRICT OPERATION fluidized compartments
AND CONTROL REQUIREMENTS; (Fig. 5-25) can get even
drying and relatively
MULTI-SEPARATELY FLUIDIZED
low flow resistance.
COMPARTMENTS(PLUG FLOW DRYERS)
HAVE COMPLEX STRUCTURES AND
GREAT FLOW RESISTA
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(3)PNEUMATIC CONVEYING DRYERS
Characteristics: 1)Great
F eed
F irst Section
Second Section
Room f or separating solids
Cleaned air
Feed E x haust air

contacting area between


First Section
Second Sect ion
Room f or separat ing solids
Cleaned air
Ex haust air

air and solids;Higher


heat transfer and mass
Feed
Feed First Section
Second Section
First Section
Room for separating solids
Second Section
Cleaned air
Room f or separating solids
Ex haust air
Cleaned air Feed

transfer rates; Short


Exhaust air First Sect ion Feed
Second Section First Section
Feed
Room f or separating solids Second Section
First Section
Cleaned air Room for separating solids
Second Section
Feed
Exhaust air
Room for separating solids Cleaned air
First Section
Cleaned air Exhaust air

drying time(0.5~2s).
Second Section
Exhaust air Room for separating solids
Cleaned air
Exhaust air

Feed

2)Stable operation and


First Section
Second Section
Room for separating solids
Cleaned air

fine product quality.


Exhaust air Feed
First Section
Second Section
Room for separating solids
Cleaned air
Exhaust Feed
air
First Section
Second Section
Room for separating solids
Cleaned air
Exhaust air

3)Applying to thermally sensitive and easily


oxidized materials.
Defects: Materials easily broken; great flow
resistance; high drying duct. (about 30m)

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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
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.
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.
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.
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.
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.
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
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.
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.
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.
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
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.
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.
DRYER FOR SLURRY AND SUSPENSION
SPRAY DRYER
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).
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.
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).
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
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
Thanks