Drying freeze-drying

Freeze drying pharmaceuticals uses a process called lyophilization to lower the temperature of the product to below freezing, and then a high-pressure vacuum is applied to extract the water in the form of vapour. The vapour collects on a condenser, turns back to ice and is removed.

1. DRYING 3 Md. Saiful Islam BPharm, MSc North South University Fb Group: Pharmacy Universe

2. FREEZE DRYING

3. DEFINITION Freeze drying is simply a conduction drying method that is operated under vacuum followed by heat transfer in the dryers. Freeze drying is also known as sublimation drying or lyophilization or cold drying. This method is known as freeze drying due to the state of the material while it is known as sublimation due to the mechanism of drying.

4. BASIC PRINCIPLE Sublimation drying consists simply of reducing both the temperature & pressure below the triple point . As a result , any heat transferred is used as latent heat and the ice sublimes directly to the vapour state . The vapour produced is quickly removed by using power exhaust system . The triple point temperature of water is 273.1598 K (0.0098˚ C ) and the pressure is 610 N/m2 . Considerations to be taken into account: 1.The temperature must be below 0.0098˚ C /273.1598 K. The usual range is between -10 to - 30˚C. 2.Similarly,the pressure must be below 610 N/m 2 . The usual range is between 10 to 30 N/m 2 .

5. TRIPLE POINT

6. BASIC ELEMENTS 1.Freezing 2.Vacuum 3.Primary drying/Sublimation phase 4.Rate of drying 5.Secondery drying/Ordinary vacuum drying 6.Packaging

7. FREEZING Pre-freezing :The solution can be pre-frozen,that is,before the start of the drying process, and this is usually applied to large containers such as blood bottles.This can be done by two ways: і. shell freezing :bottles are rotated horizontally and slowly in a refrigerated bath. іі. vertical spin freezing

8. SHELL FREEZING

9. THE CENTRIFUGAL EVAPORATIVE FREEZING This method freeze liquids in small containers without refrigeration. It also shortens the primary drying stage. Ampoules are usually frozen in this method.

10. Vacuum To reduce the pressure sufficiently it is necessary to use efficient vacuum pumps,usually two stage rotary pump-for the small scale and ejector pump-for the large scale.

11. Primary drying During the primary drying , the latent heat of sublimation ( 2900 kJkg -1 ) must be provided & the vapour must be removed . This process consist of two things: Heat transfer : Heat transfer is critical , insufficient heat prolongs the process , which is already slow & excess heat will cause melting . So the heat transfer must be controlled since only 5 W/m 2 K is needed in all cases. Vapour removal: The vapor formed must be removed continually to avoid a pressure rise that would stop sublimation. On the small scale , vapor is absorbed by a desiccant such as phosphorous pentoxides , or it is cooled on a small condenser with solid carbon dioxide . On the large scale , vapour is commonly removed by pumping . Ejector pumps are most satisfactory for this purpose.

12. Rate of drying The rate of drying in freeze drying is very low,the ice being removed at a rate of about 1 mm depth/hour

13. Secondary drying The primary drying process leaves products with about 0.5 % moisture in the solid and this is removed by secondary drying process . The usual method is to raise the temperature often 50 to 60 C.The use of such a high temperature may seem surprising in view of the remarks in the primary drying , but the secondary drying period is ordinary vacuum drying, the product is virtually free from moisture & the risk of hydrolysis becomes negligible.

14. Packaging In view of packaging of the freeze dried products , special care must be taken to ensure protection from moisture. Containers should be closed ensuring no contact with the atmosphere for example ampoules are sealed under vacuum. Or, the closure of containers must be carried out under controlled atmospheric conditions.

15. Freeze drying process: Freezing ↓ Vacuum ↓ Primary drying/sublimation phase. ↓ Secondary drying/Ordinary vacuum drying.

16. ↓ Packaging ↓ Storage ↓ Reconstitution phase

17. Freeze dryers: There are essentially three categories of freeze dryers: rotary freeze dryers, manifold freeze dryers, And, cabinet freeze dryers. Rotary freeze dryers are usually used with liquid products, such as pharmaceutical solutions and tissue extracts . Manifold freeze dryers are usually used when drying a large amount of small containers. Cabinet freeze dryers are the most common, because they can be used to dry a variety of materials.

18. Freeze-drying Equipment:- fig:- Unloading trays of freeze-dried material from a small cabinet-type freeze dryer.

19. fig:- Model FD200(invented by cuddon engineering innovation,24 hour drying cycle,using for general and pharmaceutical purpose.)

20. Application/Uses: Pharmaceutical view: * This method is applied only to biological products-antibotics(other than penicillin),blood products ,vaccines such as BCG,yellow fever,small pox. * Enzyme preparations-hyaluronidase * Microbiological cultures. In Food industry: Freeze dried ice cream,instant coffee etc. Also frequently used in different technological industry. Very recently,some taxidermies have begun using freeze drying to preserve animals

21. Advantages: Drying takes place at very low temperature , so that enzyme action is inhibited, and decomposition particularly hydrolysis is minimized. The solution is frozen so that the final dry product is a network of solid occupying the same volume as the original solution . Thus the product is light and porous. The porous form of the product gives ready solubility. There is no concentration of the solution prior to drying . Hence, salts do not concentrate and denature proteins as occurs with other drying methods. Under high vacuum , there is no contact with the air and oxidation is minimized.

22. Disadvantages: The porosity,ready solubility,and complete dryness yield a very hygroscopic product. The process is very slow. This process also uses complicated plant which is very very expensive. Packaging requires special attention/conditions

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