about freeze drying

1. Freeze Drying
Suhail Ahmed
Department of Quality
Assurance
suhailahmed523@yahoo.in

2. Freeze Drying
 Freeze drying or lyophilization, is a critical unit
operation in pharmaceutical development and
manufacturing because it allows removal of water
from heat sensitive materials at low temperature,
thereby avoiding thermal damage .
 Freeze drying as an industrial process was
introduced at around the time of world war 2 for
production of freeze dried human plasma,
followed by manufacture of antibiotics, steriods,
and injectable vitamins.

3. Principle
 Based on Sublimation, where water passes directly
from solid state (ice) to the vapor state without
passing through the liquid state.
 Sublimation of water can take place at pressures and
temperature below triple point i.e. 4.58 mm of Hg
and 0.0098 degree Celsius.
 Material to be dried is first frozen and then subjected
under a high vacuum to heat; frozen liquid sublimes
leaving only solid ,dried components.

4. Phase diagram of water
Lyophilization is carried out below the triple point to enable conversion of
ice into vapor, without entering the liquid phase (known as sublimation).

5.  At the triple point (0.0098°C and 4.58 mm Hg), ice , water
and water vapor coexist in equilibrium..
 If we heat the water above the triple point, the water will
change from liquid state to vapour state
 But when we heat the water below this triple point, then
the water will change from solid state to vapour state
directly
 Conversion of ice into water vapour is called as
sublimation
 It is the basic principle of freeze drying process

6. Steps in Freeze Drying
Pretreatment
Freezing
Primary Drying
Secondary Drying

8. Prepreparation and Pre-treatment:
Method of treating the product prior to freezing include
concentrating the product, decreasing a high-vapor pressure
solvent, or increasing the surface area.
Pre freezing to solidify water:
The aqueous solutions packed in vials, ampules or bottles are
cooled by using cold shelves (around - 50˚C). Normal cooling
rates in pre-freezing stage is around 1-3 ˚k/min. Thickness of
the frozen material affects the rate of drying, thinner is the
layer, higher is the drying rate.

9. Primary drying (sublimation of ice under
vaccum):
Once the solution is frozen, during primary drying vacuum is
applied of the value of about 0.5 bar. The temperature is
linearly increased to around 30˚C in a span of 2 hr and temp. is
maintained constant during primary and secoundary drying. It
removes easily removable moisture. During this stage around
98 to 99 % water is removed. This is followed by secoundary
drying.
 Secoundary drying (Removal of residual
moisture under high vacuum):
This stage removes (sublime) the moisture which is difficult to
remove. During primary drying Temp. is maintained constant
at 30˚C. But now vacuum is lowered to 0.07 bar. The rate of
drying is very low it takes around 10 to 20 hours

10. Packing:
Closing of vials or bottles occurs in the drying plant after the
vacuum has been broken by dry inert gas. Removal of residual
moisture takes considerable time. In drying sera containing
10% of solid has shown that 80% of the total drying period is
required to remove 95% of the total moisture, whereas 90% of
total drying period is required to attain 1% residual moisture
and remaining 10 % of the drying time is required to remove
next 0.5 %.

11. Equipment
The main components of freeze drying equipment
are:
 Refrigeration System
 Vacuum System
 Control System
 Product Chamber or Manifold
 Condenser

12.  Refrigeration system - cools the condenser located
inside the freeze dryer. It also cool shelves in the
product chamber for the freezing of the product.
 Vacuum system - consists of a separate vacuum
pump connected to an airtight condenser and attached
product chamber.
 Control systems - include temperature and pressure
sensing ability. Advanced controllers use the
programming of a complete “recipe” and monitor freeze
drying process. It depends on the application and use.

13.  Product chambers - a larger chamber with a
system of shelves on which to place the
product.
 Condenser – It is to attract the vapors being
sublimed off of the product. The sublimated ice
accumulates in the condenser. temperature of
the condenser substantially below the
temperature of the product

14. APPLICATIONS
Pharmaceutical and biotechnology
1. Pharmaceutical companies 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, the material can be
easily stored, shipped, and later reconstituted to
its original form for injection.

15. Food Industry
1. Freeze-drying is used to preserve food and make it
very lightweight.
2. The process has been popularized in the forms of
freeze-dried ice cream, an example of astronaut
food.
Technological Industry
1. In chemical synthesis, products are often freeze-
dried to make them more stable, or easier to
dissolve in water for subsequent use.

16. 2. In bio- separations, freeze-drying can be used also as
a late-stage purification procedure, because it can
effectively remove solvents.
Advantages:
 Chemical decomposition is minimized.
 Removal of water without excessive heating.
 Enhanced product stability in a dry state.
 Ease of processing a liquid, simplifies aseptic
handling.
 More compatible with sterile operations than dry
powder filling.

17. • Under high vacuum, there is no contact with air
and oxidation is minimised.
Disadvantages:
 Increased handling and processing time.
 Volatile compounds may be removed by vacuum.
 The process is very slow and uses complicated
plant, which is very expensive.
 the porosity, ready solubility and complete
dryness yields a very hygroscopic product.