DRYING
Ls dx
R
A dt
W Ws
Xt
Ws
Xt = W/ LS
X Xt X *
LIMITATIONS OF CONVENTIONAL
DRYERS
non-uniform product quality due to overdrying/
under-drying caused by long or inadequate or non-
uniform exposure to the drying medium
long drying times due to low contacting efficiency
between the drying medium and solids being dried
harder texture owing to case hardening of the
product surface caused by over-drying etc.
This gives rise to low drying performance and high
operating costs
TWO DIFFERENT PROCESSES IN DRYING
Batch processes.
Continuous process.
BATCH PROCESSES
1. HOT AIR OVENS
Ovens operating by passing hot air over the surface
of a wet solid that is spread over trays arranged in
racks provide the simplest and cheapest dryer.
BATCH PROCESSES
2. VACUUM AIR OVENS
This equipment is a good example of conduction drier. The
vacuum oven consists of a jacketed vessel to withstand
vacuum within the oven. The oven can be closed by a door.
The oven is connected through a condenser and liquid receiver
to a vacuum pump.
Operating pressure can be as low as 0.03-0.03 bar, at which
pressures water boils at 25-35 C.
top spray
Bottom spray
Tangential spray
KEY PROCESS VARIABLES
air conditions:
The powder bed is fluidized by inlet air, and it is
important to keep sufficient fluidization throughout
the process, otherwise the bed may collapse.
equipment related factors
Nozzle, Wurster
Formulation variable
Starting material property
Granule/particle size
Type of binder
Anti electrostatic agent
ADVANTAGES OF FLUIDIZED-BED DRYING
1- Efficient heat and mass transfer give high drying rates, so that
drying times are shorter than with static-bed convection driers.
Economic, heat challenge to thermolabile materials is minimized.
2-The fluidized state of the bed ensures that drying occurs from
the surface of all the individual particles and not just from the
surface of the bed. Hence, most of the drying will be at constant
rate and the falling rate period is very short.
3-The temperature of a fluidized bed is uniform and can be
controlled precisely.
4-The turbulence in a fluidized bed causes some attrition to the
surface of the granule. This produces a more spherical free-
flowing product.
5-The free movement of individual particles eliminates the risk of
soluble materials migrating, as may occur in static beds.
DISADVANTAGES OF FLUIDIZED-BED
DRYING
How?
Freeze the material
Lower the pressure
Increase the temperature
slightly
LYOPHILIZATION
18 Baxter Confidential
Courtesy of Samir U. Sane, Ph.D., Genentech, Inc.
19
Product temperature
lower than shelf
temperature during
primary drying because
energy is consumed as
ice sublimes to vapor.
20 Baxter Confidential
WHY LYOPHILIZATION OF
PHARMACEUTICALS
Advantages:
1. Stability: Aqueous Stability
To make sure that no more than 10% degradation in 2-4
years
Thermal Stability : High temperature conventional drying
may not be suitable
2. Improved Product Characteristics:
Improved kinetic solubility (because of porosity and very
large surface area)
Usually freeze-dried product is amorphous
3. Other Advantages:
Shipping advantage (low weight)
Less interaction with primary package of highly alkaline
solutions
Less problems with glass delamination
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WHY LYOPHILIZATION OF
PHARMACEUTICALS
Advantages: cont.
4. Accuracy of dosage
Ease of filling complex formulation as a solution
Doses as low as 0.1 mL (vaccines, GF etc.)
5. Well controlled headspace
Nitrogen, Argon (oxygen and some time Freon too)
Vacuum
6. Ease of Operation:
Liquid filling operation: Automatic, accurate, well controlled
(well established)
In-line sterilization filtration in the final container
Points to Consider
Triple point
Sublimation occurs between the solid and the vapor phase regions.
Since only two phases are present (solid line), solid ice and the vapor ice are in
equilibrium.
The diagram also says that once Temp of ice is fixed, the vapor pressure over
ice is automatically fixed, and vice-a-versa.
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CONTINUOUS DRYERS
1. SPRAY DRYER
The spray dryer 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 a solid particle.
1-The droplets are small, giving a large surface area for heat
transfer, so that evaporation is very rapid. The actual drying
time of a droplet is only a fraction of a second, and the overall
time in the dryer is only a few seconds.
2- The thermal efficiency is high, as the drier casing and the air
remain cool. Most of the microwave energy is absorbed by the
liquid in the wet material.