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Lyophilization S. M. Mosghtofa Fariadi Rubal
Sr. executive,R & Dh
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Lyophilization
Andez mountains
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Definition
Lyophilization or freeze drying is aprocess in which water is removed from
a product after it is frozen and placedunder a vacuum
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Application
Freeze drying is a widely used method for
the stabilization of degraded substances:
- microorganisms
- foods - biological products and
- pharmaceutical products.
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The advantages of lyophilization
1.Product is stored in dry state- stability problems are reduced
2.Product is dried without elevated temperatures-heat sensitiveproducts
3.Good for oxygen and/or air-sensitive drugs.
4.Rapid reconstitution time.
5.Constituents of the dried material remain homogenously dispersed.
6.Product is process in liquid form that ensures uniformity
7.Sterility of product can be achieved and maintained.
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Disadvantages of lyophilization
1.Volatile compounds may be removed by high vacuum.
2. Single most expensive unit operation.
3. High energy costs (2-3times more than othermethods).
4. Long process time.
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Related Terminology
Eutectic Point: The lowest temperature at which a substance willmelt.
Triple Point: The temperature at which a substance can remain insolid, liquid and gaseous form.
Sublimation:Vaporization or evaporation wholly from a solidphase to gas without melting.
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FREEZING PRIMARY DRYING
OR ICE SUBLIMATION
SECONDARY DRYING
OR WATER DESORPTION
FREEZE DRYING
FREEZE DRYING PROCESS
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The lyophilization process
The lyophilization process generally includes thefollowing steps:
Dissolving the drug and excipients in a suitablesolvent,
Sterilizing the bulk solution by passing it through a0.22 micron bacteria-retentive filter.
Filling into individual sterile containers and partially
stoppering the containers under aseptic conditions.Transporting the partially stoppered containers to
the lyophilizer and loading into the chamber underaseptic conditions
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Typical lyophilization process
Washing
Sterilization
Depyrogenation
Component preparation
Solvent
Excipients
Active
Sterile filteration
Compounding
Filling
Partialstoppering
Tray loading
Filling
Freezing
Sublimation
Desorption
Full stoppering
Freeze drying
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The lyophilization process
Freezing the solution .
Freezing
In this step, it is important to cool the materialbelow its triple point
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The lyophilization process
Applying a vacuum to the chamber and heating theshelves in order to Evaporate the water from thefrozen state.
Primary drying
During the primary drying phase, the pressure islowered and enough heat is supplied to the materialfor the water to sublime.
Secondary drying
The secondary drying phase aims to removeunfrozen water molecules, since the ice was removedin the primary drying phase.
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The lyophilization process
Complete stoppering of the vials usually by hydraulicor screw rod stoppering mechanisms installed in thelyophilizers.
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The lyophilization process
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Lyophilizer Machine
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DRYING
CHAMBER
CONDENSOR VACCUM
PUMP
REFRIGERATION
SYSTEM
CONTROL
FACILITIES
FREEZE DRYER
Structure of freeze dryer
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Basic Principles of lyophilization process
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QUALITY REQUIREMENTS
The most important objective in the developing afreeze
dried product is to assure the quality requirements as:
the original chemical or biological potencyafterreconstitution
rapid and complete dissolution
appropriate residual moisture level, and
acceptable cake appearance. This requirements have to be met not only initially
but throughout the shelf life of the product
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Finished product inspection
Melt back - generally the lyophilized drug is in formof cake but the cake may collapse due to change fromsolid to liquid state because of incompletesublimation.
Poor solubility - this may decrease the potency of thedrug.
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The development of a suitable formulation
The development of a suitable formulation and a freeze-drycycle requires knowledge of some basic properties, suchas:
eutectic temperature
temperature effect on solubility
thermal properties of the frozen solution
degree of super-cooling
heat transfer properties of the freeze-dryer shelves, the metal trays, the containers and the frozen product
equipment design and equipment capability.
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OBJECTIVE OF FORMULATOR
Overall cycle to be carried out in the least amount oftime, while providing a stable and efficaciousproduct which:
- contains a low moisture content,
- undergoes rapid reconstitution, and
- possesses the desired appearance.
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Diagram of Water vapor
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Factors Affecting Efficiency
sample size surface area of the sample
thickness of the sample
sample characteristics eutectic temperature
solute concentration
instrument factors
condenser temperature
vacuum
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Lyophilization Container Requirements
The container in which a substance is lyophilizationmust permit -
thermal conductivity, be capable of tightly sealed at the end of
lyophilization cycle and
minimize the amount of moisture to permeate itswalls and seal.
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CONCLUSIONS
Thank you for attention