Lyophilized product production and facilities for parenterals

Industrial pharmacy assignment

1. Maharishi Dayanand University Rohtak Department of Pharmaceutical Science Industrial pharmacy assignment Formulation of lyophilized product production and facilities for Parenterals Submitted to Mrs. Prerna Kaushik Submitted by Deepender
Roll no 1444 B.Pharm 5thsem Batch- A

2. Definition A stabilizing process in which a substance is first frozen and then the quantity of the solvent is reduced, first by sublimation (primary drying stage) and then desorption (secondary drying stage) to values that will no longer support biological activity or chemical reactions. 2

3. Principle 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. 3

4. Objective of lyophilized process To preserve the biological activity of a product.

To reduce the product weight to lower the transportation cost.

• To extend the shelf life or stability. To dry thermolabile materials.

• To eliminate the need for refrigerated storage.

. To get accurate, sterile dosing into the final product container. 4

5. Processing Fundamental process steps are:
1. Freezing: the product is frozen. This provides a necessary condition for low temperature
2. Vacuum: after freezing, the product is placed under vacuum. This enables the frozen solvent in t product to vaporize without passing through liquid phase, a process known asSUBLIMATION.
3. Heat: Heat is applied to the frozen product to accelerate sublimation.
4. Condensation: Low-temperature condenser plates remove
the vaporized solvent from the vacuum chamber by
converting it back to a solid. This completes the process 5

6. • Freezing the product solution to a temperature below its
eutectic temperature.
Decrease the shelf temperature to -50°c.
Low temperature and low atmospheric pressure are
maintained. Freons are used as refrigerant.
Formation of ice crystals occurs. The rate of ice crystallization define the freezing process and efficiency of primary drying. Freeze Drying 6

7. Primary Drying (Sublimation) 7 Heat is introduced from shelf to the product under graded
control by electrical resistance coils or circulating silicone.
The temperature and pressure should be below the triple point of water i.e., 0.0098°C and 4.58mmHg.
The driving force is vapor pressure difference between the evaporating surface and the condenser.
Easily removes moisture up to 98% to 99%.

8. Packaging After drying the vacuum is replaced by filtered dry air or nitrogen to establish atmospheric pressure
Ampoules are sealed by either tip sealing or pull sealing method
Vials and bottles are sealed with rubber closures and aluminum caps 8

9. Freeze Dry Product Characteristics • Sufficient strength

• Uniform color

• Sufficiently dry

• Sufficiently porous

. Sterile

• Free of pyrogens and particulates

• Chemically stable both in dry state and reconstituti 9

10. Advantages of Lyophilization Removal of water at low temperature

Thermolabile materials can be dried.

.Compatible with aseptic operations

More precise fill weight control

Sterility can be maintained. Reconstitution is easy 10

11. Disadvantages of Lyophilization 11 Many biological molecules are damaged by the stress associated with freezing, freeze-drying, or both. The product is prone to oxid due to high porosity and large surface area. Therefore the product should be packed in vacuum or using inert gas or in a container impervious to gases. Cost may be an issue, depending on the productLong time process

12. 12 Production Facilities of Parenterals: The production area where the parenteral preparations are manufactured can be divided into five section 1 . Clean up area: It is not aseptic area All the parenteral products must be free from foreign particles and microorganism Clean up area should be withstand moistute, dust & detergent. This area should be kept clean so that contamination may not carried out into aseptic area 2. Preparation area: In this area the ingredients of the parenteral preparation are mixed & preparation is made for filling operation It is not essentially aseptic area but precaution are required to prevent anycontaminati on from outside. 3. Aseptic area: The parenteral preparation are filtered filled into final container & sealed should be in aseptic area. The entry of personal into aseptic area should be limited & through an air lock. Celling, wall & floor of that area should be sealed

13. Quarantine area After filling, sealing & sterilization the parental product are held up in quarantine area. Randomly samples were kept for evaluation.
The batch or product pass the evaluation tests are transfer into finishing or packaging area. Finishing & packaging area: Parenteral products are properly labelled and packed.
Properly packing is essential to provide protection against physical damage. • Ampoules should be packed in partition boxes. 13

14. References 14 http://www.slideshare.net/ceutics1315/lyophilization-39635366?from_m_app=android http://www.slideshare.net/sangrammaskar/preparation-of-large-volume-and-small-volume-parenteral-235629944?from_m_app=android

15. Thanks! Any questions? 15