Lyophilization of Parenterals final .docx.pptx

7/30/2019 Lyophilization of Parenterals final .docx.pptx

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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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Freezing the solution .

Freezing

In this step, it is important to cool the materialbelow its triple point


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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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Complete stoppering of the vials usually by hydraulicor screw rod stoppering mechanisms installed in thelyophilizers.


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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

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