lyophilization technology 03/2011. 03/03/2011lyophilizer tech. summary | 03 march 20112 what is...

Lyophilization Technology

03/2011

03/03/2011 Lyophilizer Tech. Summary | 03 March 2011 2

What is freeze-dryingWhy is it used

A means of preservationUsed to provide a stable product that may

be stored for a long time.Applied to products and materials that may

change if heat is applied.A dehydration processInvolves sublimationA batch process and can take a long time.

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Advantages of Lyophilization

Proteins thermally sensitive can be dried. Products sensitive to oxygen can be sealed in N2. In a vial the fill volume is accurate giving better dosage

control than powder filling. The second drying step can be controlled to give

excellent long term storage properties. No change in moisture level during storage. More control of the environment compared with other

methods. Products are more stable after lyophilizing.

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What kind of products can be freeze-driedNon-biological products

heat-labile chemicalsNon-living bio products (majority)

enzymes, hormones, antibiotics, vitamins, blood products, antibodies,

vaccines, pharmaceuticals bone and body tissues for surgical/medical use, foodstuffs

Living organismsMiscellaneous materials

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Required from a lyophilized material?

Dried to the right moisture contentEthically acceptableCosmetically RefinedActive!StableCake likeClean

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-100

-80

-60

-40

-20

0

20

40

60

0 5 10 15 20 25 30

Refrigeration VacuumSystems

EquipmentFaultfinding

Tem

pera

ture

Freeze DryerDesign

CycleDevelopment

Critical temperature

Shelf temperature

Product temperature

Pre-Freezingstage

Holdingperiod Primary

dryingSecondaryDrying

Time

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The Process for lyophilization1. Solution preparation, Depth in a vial is 0.5 inch.

The water based products are typically < 10% solutions.

2. Freezing, Freeze to -40 0C. Freezing below a critical temperature before the drying process. Kept at its lowest temperature for a given period to ensure all the material is frozen. Form large, contiguous ice crystals. Be frozen quickly. Freeze rate is 10C/minute

3. Primary Drying. Supply of heat and the pressure used. Involve Sublimation

4. Secondary Drying5. Stoppering (vials)6. Final condition

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Sublimation Solid (ice) to a vapor. An energy intensive process Latent heat of sublimation of ice

2800 kJ/kg (1200Btu/lb). In Lyophilizing step, product must go from a

solid form to a vapor. For sublimation to occur, supply the energy.

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Phase Diagram for Pure Water760 torr

100 0C

4 torr

Liquid

Triple point

Vapor

Solid

Product Temp.

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