Lyophilization, or freeze drying, is a process that removes water from a frozen product under vacuum conditions, allowing ice to change directly from solid to vapor without passing through the liquid phase. The process consists of three main steps - freezing, primary drying where ice sublimates under vacuum, and secondary drying to remove residual moisture. Lyophilization is useful for drying thermolabile compounds as it occurs at low temperatures, resulting in a stable dry powder that can be reconstituted for use.

1. LYOPHILIZATION TECHNOLOGY
Prepared by
Dr. Kandekar Ujjwala Y.
M. Pharm. PhD.
JSPM’s Rajarshi Shahu College of Pharmacy and Research, Tathwade,
Pune
PROCESS AUTOMATION IN
PHARMACEUTICAL INDUSTRY

2. Lyophilization or freeze drying:
It is a process in which water is removed from a product after it is frozen and placed under a
vacuum, allowing the ice to change directly from solid to vapor without passing through a liquid
phase.
Lyophilization is carried out using a simple principle of physics sublimation. Sublimation is the
transition of a substance from the solid to the vapour state, without first passing through an
intermediate liquid phase.
Lyophilization is performed at temperature and pressure conditions below the triple point, to enable
sublimation of ice.
The entire process is performed at low temperature and pressure by applying vacuum, hence is
suited for drying of thermolabile compounds.
The concentration gradient of water vapour between the drying front and condenser is the driving
force for removal of water during lyophilization.
The process consists of three steps:
• Pretreatment
• Freezing
• Primary drying (sublimation)
• Secondary drying (desorption).

3. • Pretreatment:
• Dissolving the drug and excipients in a suitable solvent, generally water for
injection.
• Sterilizing the bulk solution by passing it through a 0.22 micron bacteria-
retentive filter.
• Filling into individual sterile containers and partially stoppering the
containers under aseptic conditions.
• Vials are partially stoppered with special slotted rubber closure that allows escape
of water vapour, when the stopper is inserted half way into the neck of vial.
• Vials are transferred under aseptic condition into drying chamber.
• Trays of the product are placed on shelves containing internal channels allowing
circulation of silicon oil or another suitable heat transfer fluid.
• Shelves may be pre chilled depending on solution stability of product. Temperature
measuring device is placed in chamber.

4. 1. Pre-freezing to solidify water :-
Vials ampoules or bottles containing aq. Solution is packed
Frozen in cold shelves(-50 degree c)
Normal cooling rate is about 1-3k/min. So that large ice crystals with relatively large
holes are formed to give porous product.

5. 2. Primary Drying ( sublimation of ice under vacuum)
Material to be dried is spread on large surface for sublimation
temp & pressure should be below
triple pt of water( 0.0098 degree C
& 0.533kpa i.e. 4.58mm Hg)
When water alone present vaccum is applied to about 3mm Hg on
frozen sample, temp increased to about 30 degree C in 2 hrs
heat supplied
Ice sublimes directly into vapour state (heat controls the movement of
ice layer inwards)

6. As soon as vapour molecules are formed these are removed as drying processes
Thickness of frozen layer decreases & thickness of partially dried solid increases.
 Primary drying stage removes easily removable moisture.
98% of water is removed.

7. 3. Secondary Drying
Traces of moisture are removed
temp raised to 50-60 degree C
vacuum lowered i.e. 50mm Hg
Drying rate is very low, it takes about 10-20 hrs
when product is sufficiently dry
Vials stoppered in place within the dryer by hydraulic compression of shelf stack,
which pushes stopper to the fully inserted position.

9. The advantages of lyophilization include:
• Ease of processing a liquid, which simplifies aseptic handling
• Enhanced stability of a dry powder
• Removal of water without excessive heating of the product
• Enhanced product stability in a dry state
• Rapid and easy dissolution of reconstituted product
Disadvantages of lyophilization include:
• Increased handling and processing time
• Need for sterile diluent upon reconstitution
• Cost and complexity of equipment
Application:-
Steroid, enzymes.
Human tissue, arteries & corneal tissue.
Bacterial & viral cultures