Process validation of tablets, capsules and parentrals

Modern Pharmaceutics

1. Process Validation of Tablets, Capsules and Parenterals Under the Guidance of Dr . Y. Indira Muzib M. Pharmacy, Ph. D Submitted by K. Bhanu Sri Chandana M. Pharmacy 1 st Year Dept. of Pharmaceutics

2. Contents : Validation Process Validation Process Validation of Tablets Process Validation of Capsules Process Validation of Parenterals References

3. Validation is a systematic approach to identify, measure, evaluate, document and re-evaluate a series of critical steps in the manufacturing process which requires control to ensure a reproducible final product. Validation : Validation is documented act of proving that any procedure, process, equipment, material, activity or system.

4. Process Validation : Process Validation is a process of establishing a documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and Quality Standards. According to EMEA, “Process validation can be defined as documented evidence that the process, operated within established parameters , can perform effectively and reproducibly to produce a medical product meeting its predetermined specifications and quality attributes”

5. Importance of Process Validation Government regulation Rapid automation Improved employee awareness Easier maintenance of equipment Increased output Reduction in quality cost Less failures of process thus less complaints Process optimization

6. Types of Process Validation 1. Prospective validation 2. Retrospective validation 3. Concurrent validation 4. Revalidation

7. PROCESS VALIDATION OF TABLETS : Tablets: Tablets are defined as “ Unit solid dosage forms containing one or more active ingredients with or without excipients which are prepared by compression” . Some of the common excipients used in the tablet formulation are Binders, Diluents, Glidants, Lubricants, Disintegrating Agents, Sweetening Agents etc.

8. Manufacturing of Tablets API + Primary Excipients (Diluents and Binding agents) Mixing Granulation Drying Sieving Packing Compression Addition of Secondary Excipients (Lubricants and Disintegrating Agents)

9. Validation of Tablets 1. Mixing or Blending The mixing or blending is an unit operation that may occur once or several times during the tablet manufacture. Tumble mixer Planetary mixer Pneumatic mixer

10. Parameters to be considered are: Mixing or blending technique Mixing or blending speed  Mixing or blending time Drug uniformity Excipient uniformity Lubricant Colour Equipment capacity/load

11. 2. Granulation Granulation is a process in which the powder particles are made to adhere to form large, multiparticle entities. Granulation is of two types. Dry Granulation Wet Granulation - Binder addition, Binder concentration, Amount of binder solution/granulating solvent, Binder solution/granulating solvent addition rate, Mixing time, Granulation end point

12. 3. Milling The parameters to be considered for validation in milling are: Equipment size and capacity  Screen size: Mill speed Feed rate

13. 4. Drying Changing dryer techniques could affect some of the tablet properties such as hardness, disintegration, dissolution, and stability. Parameters to consider during drying are: Inlet/outlet temperature Airflow Moisture uniformity Equipment capability/capacity

14. 5. Compression The materials being compressed will need to have adequate flow and compression properties. Inadequate flow can result in “rat holing” in the hopper and/or segregation of the blend in the hopper/feed frame . Factors to consider during compression are: Tooling Compression speed Compression/ejection force

15. 7. Coating: Key areas to consider for tablet coating includes: Tablet properties Equipment type Coater load Pan speed Spray guns Application/spray rate g. Tablet flow h. Inlet/outlet temperature and airflow i . Coating solution j. Coating weight k. Residual solvent level

16. Appearance testing of the tablets is critical during the coating operation. Items to look for include the following: 1. Cracking or peeling of the coating. 2. Intagliation fill-in. 3. Surface roughness. 4. Color uniformity .

17. In-Process Tests 1.  Moisture content of “dried granulation” 2. Granulation particle size distribution 3.  Blend uniformity 4.  Individual tablet Weight 5.  Tablet hardness 6.  Tablet thickness 7.  Disintegration

18. Finished Product Tests 1. Appearance 2. Assay 3. Content uniformity 4. Tablet hardness 5. Tablet friability 6. Dissolution

19. PROCESS VALIDATION OF CAPSULES Capsules: Capsules are oral solid dosage forms in which the medicament is enclosed in a shell which is generally made up of Gelatin. Based on Gelatin, the capsules are of two types. Hard Gelatin Capsules Soft Gelatin Capsules

20. Validation of Capsules Capsule Composition Capsule Shell Capsule Shell Contents B. Process Evaluation and Selection C. Encapsulation Encapsulation type Encapsulation speed

21. PROCESS VALIDATION OF PARENTERALS Parenterals: Parenterals are the sterile solutions or suspensions of a drug which may consists of one or more active ingredients that are intended to administer through an injection or an infusion The steps involved in Validation of Parenterals are: Sterilization Manufacturing Packaging

22. An International Edition on Pharmaceutical Process Validation by Robert A. Nash and Alfred H. Wachter A Review on Industrial Process Validation of Tablet Dosage Form A Review on Validation of specific dosage forms by H. Sai Priyanka Process validation of tablet dosage form: A comprehensive review by Kiranbala Jain and Meenakshi Bharkatiya A review on Process Validation of capsules An article on Industrial P rocess Validation of Sterile Products References: