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 1st 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:
a) Mixing or blending technique
b) Mixing or blending speed
c) Mixing or blending time
d) Drug uniformity
e) Excipient uniformity
f) Lubricant
g) Colour
h) 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.
i. Dry Granulation
ii. 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:
a. Equipment size and capacity
b. Screen size:
c. Mill speed
d. 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:
a. Inlet/outlet temperature
b. Airflow
c. Moisture uniformity
d. 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:
a. Tooling
b. Compression speed
c. Compression/ejection force

15. 7. Coating:
Key areas to consider for tablet coating includes:
a. Tablet properties
b. Equipment type
c. Coater load
d. Pan speed
e. Spray guns
f. 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.
1. Hard Gelatin Capsules
2. Soft Gelatin Capsules

20. Validation of Capsules
A. Capsule Composition
i. Capsule Shell
ii. Capsule Shell Contents
B. Process Evaluation and Selection
C. Encapsulation
i. Encapsulation type
ii. 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:
1. Sterilization
2. Manufacturing
3. 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 Process Validation of Sterile Products
References: