It have factors, Various Method, Accelerated stability testing,ICH Guidelines, Climatic Zones

1. Stability Testing of Pharmaceutical
dosage form
Prepared by
Nirmalya Dutta
M.Pharm (Pharmaceutics)
Student of Calcutta Institute of Pharmaceutical Technology and AHS

2. Content
Definition
Factors Effecting Stability
Types Of Stability studies on Drug Substances
Stability Testing Method
Accelerated Stability Testing
Method of Accelerated Stability Testing
Stability Protocol
Storage Condition
ICH Guidelines for stability studies
Climatic Zone for stability studies
Conclusion
Reference

3. Definition
As per USP Stability of Pharmaceutical product is, “extent to which a
product retains with in specified limits and throughout its period of
storage and use which mean shelf life”
Why Stability Studies is necessary?
Quality of the product.
Establish Self life for the drug product.
Storage Condition.
Determine container closure system suitability.
For chemical degradation.
Toxic products may be formed.

4. Shelf Life
 The time required for the concentration of the reactant to reduce
to 90% of its initial concentration.
𝑡90 =
(𝑎−0.9𝑎)
𝑘𝑜
where, a=initial concentration
ko= specific rate constant for zero order reaction

5. Factors Effecting Stability
Factors
Environmental
Factor
Temperature
Light
Moisture
Microbial
Contamination
Containers and
closure
Plastics
Metals
Rubbers

6. Types Of Stability studies on Drug
Substances
Physical Stability- Physical properties such as appearance, colour,
dissolution, palatability, suspendability, uniformity are retained.
Chemical Stability- It is the tendency to resists its change due to
the reactions that occur due to air, atmosphere, temperature etc.
Microbiological stability- It is tendency to resistance to the
sterility and microbial growth. This microbiological instability could be
hazardous to the sterile drug product.
Therapeutic stability- It remains unchanged
Toxicological stability- This have also no significance increase in
the toxicity occurs

7. Stability Testing Method
The stability testing procedure have been categorized into 4 types and
they are---------
1. Real time stability testing
2. Retained sample stability testing
3. Cyclic temperature stress testing
4. Accelerated stability testing

8. Real Time Stability Testing
-> It is normally performed for a long duration of time to allow significant
degradation of the product under the storage condition recommended.
->While testing the samples are collected at regular interval the data is
collected at the appropriate frequency.
Retained sample stability testing
-> If the number of samples exceeds more than 50 then they are divided
into 2 batches.
->After introducing to the market the samples of every batch are taken
which decrease from 2%-5%.
->This test help to predict the shelf life.

9. Cyclic temperature stress testing
->In this testing the sampling is considered to be conducted by a cycle
of 24 hours.
->Test of samples,minimum and maximum temp are noted based on
temperature,storage condition,chemical and physical degradation of
the product

10. Accelerated Stability Testing
Arrhenius Equation- For every 10° Increase in temperature,
the speed of reaction increases about 2-3 times
K =Ae – Ea / RT Where A= Arrhenius factor
-Ea=Energy of activation
RT=Ideal gas constant
logK=logA –Ea /2.303RT

11. Method Of Accelerated Stability
testing in dosage form
A. Freeze Thaw Test
B. Centrifugal Test
C. Shaking Test
D. Elevated Temperature test

12. Stability Testing Protocol
The Stability study Protocol should include the following Information
1. Number of batches
2. Container and closure
3. Orientation of storage of containers
4. Sampling time points
5. Test Storage Condition
6. Test Parameter

13. Storage Condition
Types of stability
studies
Storage Condition Minimum Time
Period(Months)
Long Term 25 ± 2°C and 60 ± 5%RH
or 30 ± 2°C and 65 ± 5%RH
12
Intermediate 30 ± 2°C and 65 ± 5%RH 6
Accelerated 40 ± 2°C and 75 ± 5%RH 6

14. ICH Guidelines For Stability
Studies
ICH Codes Guidelines Title
Q1A Stability testing of new drug substances and products (second
revision)
Q1B Photo stability testing of new drug substances and products
Q1C Stability testing of new dosage form
Q1D Bracketing and Matrixing Designs for the stability testing of drug
substances and products
Q1E Evaluation of stability data
Q1F Stability data package for registration applications in climatic
zones III and IV

15. Climatic Zone for Stability Study
Climatic Zone Climate Countries
I Temperate United Kingdom, Russia, USA
II Subtropical and
Mediterranean
Japan, Southern Europe
III Hot and Dry Iraq, India
IV a Hot and Humid Iran, Egypt
IV b Hot and very humid Brazil, Singapore

16. Conclusion
Stability testing is now the key procedural component in
the pharmaceutical development program for a new drug as well as
new formulation. Stability tests are carried out so that
recommended storage conditions and shelf life can be included on
the label to ensure that the medicine is safe and effective
throughout its shelf life. Over a period of time and with increasing
experience and attention, the regulatory requirements have been
made increasingly stringent to achieve the above goal in all
possible conditions to which the product might be subjected during
its shelf life.

17. Reference
1) L Lachman , K.Herbert A.; “The Theory and Practice of Industrial
Pharmacy” ; special Indian edition 2009 ; CBS Publishers and
Distribution Pvt. Ltd. ; Page No- 772 , 777 , 849
2) J.S Ptrick ; “Martin’s Physical Pharmacy and Pharmaceutical
Science”; 5th edition; published by Wolters Kluver Health (India)
Pvt. Ltd. New Delhi. Page No-332-337
3) WHO. Stability studies in a global environment. Geneva
meeting working document QAS/05.146 with comments, (2004).
4) CPMP. Guideline on stability testing: Stability testing of
existing active substances and related finished products.
CPMP/QWP/122/02, 2003.
5) K.Wolters; “Remington The science and practice of pharmacy”;
21st edition volume-2005;published in Philadelphia College of
Pharmacy and science” ;page no - 1025-1033