The document discusses the importance and methodology of stability studies for pharmaceutical products, focusing on determining shelf life, evaluating product quality, and ensuring patient safety. It outlines various types of stability, factors affecting stability, testing methods, and the responsibilities of pharmacists in managing product stability. The document emphasizes the need for controlled storage conditions and regulatory compliance to maintain the safety and efficacy of drugs throughout their shelf life.

2. STABILITY OF
FORMULATED
PRODUCTS

3. TABLE OF CONTENTS.
Introduction.
Definition of stability.
The five types of stability.
Factors affecting product stability.
Stability studies in manufacturing.
Observing products for evidence of
instability.
Responsibility of the pharmacist.
Reference.

5. Objectives
of stability
studies
ØDetermine Shelf Life: Establish the length of time a
product remains stable and effective under specified
storage conditions.
ØEvaluate Product Quality: Assess the physical,
chemical, and microbiological characteristics of a product
over time.
ØIdentify Degradation Pathways: Understand how a
product degrades or breaks down over time.
ØEnsure Patient Safety: Verify that a product remains
safe and effective for patient use throughout its shelf life
ØSupport Labeling Claims: Provide data to support
product labeling claims, including shelf life and storage
conditions.
ØSupport Product Development: Inform product
development decisions, such as reformulation or new
product development, with stability data.

6. WHY STABILITY…
• Provide a evidence on how the quality of a
drug substance or drug product varies with
time under the influence of a variety of
environmental factors such as…..
temperature, Humidity and light.
• Establish a re-test period for the drug
substance or a shelf life for the drug
product and recommended storage
conditions.
• Because physical, chemical or
microbiological changes might impact the
efficiency and security of the final product.
6

7. Where and Why?
Stability Studies are preformed on ...
 Drug Substances (DS)  The unformulated drug substance that
may subsequently be formulated with excipients to produce the
dosage form.
 Drug Products (DP)  The dosage form in the final immediate
packaging intended for marketing……. controlled and documented
determination of acceptable changes of the drug substance or drug
product

8. Importance of
stability study
Assurance to
patient that
drug is safe.
Legal
requirement to
provide data.to
protect the
reputation of
the
manufacturer
To provide a
database.to
determine shelf
life and storage
conditions
To verify that no
changes have
been introduced
in the
formulation or
manufacturing
process

9. Testing scope for
Solid dosage form
 Physical-chemical properties
– Appearance
– Elasticity
– Mean mass
– Moisture
– Hardness
– Disintegration
– Dissolution
 Chemical properties
– Assay
– Degradation
 Microbial properties
 Container closure system
properties
– Functionality tests (e.g.
extraction from blister)
9
ØPhysical-chemical properties​
– pH​
– Loss on weight​
– Color & clarity of solution​
- Sterility Tests​
ØChemical properties​
– Assay​
– Degradation products​
– Degradation preservatives​
– Content antioxidants​
ØMicrobial properties ​
- Pyrogen Testing ​
ØContainer closure system properties​
– Functionality tests​
- Leakage test
Testing scope for
Liquid dosage form

11. Stages of Stability Studies
• Stability study is performed at various stages
of the drug development process.
• There are 6 different stages:
Stage 1: Early stage, i.e., stress and accelerated
testing with drug substances.
Stage 2: Stability on pre-formulation batches.
Stage 3: stress test done on scale-up batches
Stage 4 : Accelerated and long-term testing for
registration purposes.
Stage 5 : Enduring stability testing.
Stage 6: follow up studies.

12. Types of stability
Chemical
Each active ingredient retains its chemical
integrity and labeled potency within specified
limits.
Physical
Microbiological
Therapeutic
Includes appearance, palatability, uniformity,
dissolution and suspend ability are retained.
Sterility or resistance to microbial growth is
retained according to specific requirement.
Activity remains unchanged.
No significant increase in toxicity.
Toxicologic

14. Real time stability testing
Accelereted stability testing
Retained sample stability testing
Cyclic temperature stress testing
Stability testing method

15.  Performed for longer duration of the test period in order to
allow significant product degradation under recommended
storage conditions.
 Depends upon the stability of the product which should be
long enough to indicate clearly that no measurable degradation
occurs.
Data collected
at frequency
Stability of
reference material
include the stability
of reagent as well
as consistency of
performance
To distinguish
instability from
day to to day
Real time stability testing

16.  A product is stressed at several high temp. & the amount of
heat input required to cause product failure is determined.
 This is done to subject the product to a condition that
accelerates degradation.
 This information is then projected to predict shelf life or used
to compare the native stability of alternative formulations.
Samples subjected
to stress Refrigerated Assayed
simultaneously
2. ACCELERATED STABILITY
TESTING

17.  Usual practice for every marketed product for which
stability data are reuired.
 Only one batch a year are selected.
 If the number of batches marketed exceeds 50,
stability samples from two batches are recommended
to be taken.
 Stability testing by evaluation of market samples is a
modified method which involves taking samples
already in the market place and evaluating stability
attributes.
3. RETAINED SAMPLE STABILITY
TESTING

18.  Is not a routine testing method for marketed products.
 In this method, cyclic temp. stress tests are designed on knowledge of
the product so as to mimic likely conditions in market place storage.
 The period of cycle mostly considered is 24 hours.
 The min, and max. temp. for the cyclic stress testing is recommended to
be selected on a product by-product basis and considering factors like
recommended storage temp. for the product and specific chemical and
physical degradation properties of the products.
 The test should normally have 20 cycles.
4. CYCLIC TEMPERATURE STRESS
TESTING

19. ICH
ICH stands for International Conference on
Harmonization of Technical Requirements for
Registration of Pharmaceuticals for Human use
Objectives of ICH
• Harmonization of registration applications within the
three regions of the EU, Japan and the United States.
• ICH is a joint initiative involving both regulators and
industry as equal partners in the scientific and
technical discussions of the testing procedures which
are required to ensure and assess the safety, quality
and efficacy of medicines.
● Tripartite guideline on stability testing of new drug
substances and products (Q1A) in 1993, has become
standard for stability evaluation in Japan, US, Europe.

20. ICH
CODE
GUIDELINE TITLE
Q1A Stability testing of New Drug Substances and
Products (Second Revision)
Q1B Stability testing Photo stability testing of New Drug
Substances and Products
Q1C Stability testing of New Dosage Form
Q1D Bracketing and Matrixing Designs for 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
Q5C Stability testing of Biotechnological/Biological
Products

21. Zone 1 Zone II Zone III Zone IV
( TEMPERATURE ) ( SUBTROPICAL &
MEDITERRANEAN)
( HOT & DRY ) (HOT & HUMID)
• United
kingdom,
• Northern
Europe,
• Russia,
• United states.
Long term testing
conditions –
21ºC/45 % RH
• Japan
• Southern
Europe.
Long term
testing
conditions-
25ºC/60% RH
• Iraq,
• India
Long term
testing
conditions-
30ºC/35 % RH
• Iran,
• Egypt.
Long term
testing
conditions-
21ºC/45 % RH
Climatic zones for stability testing

23. Drug substances/Product- intended for storage in Freezer
Study Storage condition Minimum time period
covered by data at
submission
Long term -20°C ± 5°C 12 months
Drug products - General case
Study Storage condition Minimum time period
covered by data at
submission
Long term 25°C ± 2°C / 60% ± 5% r.h. or
30°C ± 2°C / 65% ± 5% r.h.
12 months
Intermediate 30°C ± 2°C / 65% ± 5% r.h. 6 months
Accelerated 40°C ± 2°C / 75% ± 5% r.h. 6 months
Climatic Zones / Storage conditions

24. Stability chamber room

25. STABILITY STUDIES
IN MANUFACTURING

26. Determining effect of temperature, light, trace metals, pH,… etc.
Formulation is prepared. (one or more):
Regarding: preparation, packaging, storage… etc.
Samples are assayed.
Regarding: potency, physical change, microbial resistance… etc.
MAINLY BIOAVAIABILITY.
Selection of formulation; containers, storage conditions and expiry
date.

27. STABILITY STUDIES FOR PHARMACEUTICAL PRODUCTS
TABLET
• Stable tablets retain their original size ,shape , weight ,roughness ,colour variation ,
cracking under normal handling and storage conditions throughout their shelf life.
• FRIABILITY TEST : studies revel the physical instability if any in tablet.
Maximum weight loss should not be more than 1%.
• HARDNESS TEST : shows resistance to crushing.
• COLOR STABILITY : by colorimeter , reflectometer with heat , sunlight and intense
artificial light.
• Uniformity of weight , odor , texture , drug and moisture content , humidity effects are
also Studied during a tablet test.
27

28. Tests Metho
d
SOP#
Specification
(Low/High)
Time (Months)
appearance 0 3 6 9 etc.
Color
Degradation
Assay
Dissolution
Clarity
Stability Raw Data format

29. AFTER REGISTRATION…
Once the pharmaceutical product has been
registered, additional stability studies are
required whenever variations that may affect
the stability of the active pharmaceutical
substance or pharmaceutical product are made,
such as major variations like the following:
a. Change in the manufacturing process.
b. Change in the composition of the
pharmaceutical product.
c. Change of the immediate packaging.

30. RESPONSIBILITY
OF PHARMACISTS

31. Pharmacists help to ensure that the products under their supervision
meet acceptable criteria of stability by :
Dispensing oldest stock first and observing expiration dates.
Storing products under the environmental conditions stated in the individual
monographs, labeling, or both.
Observing products for evidence of instability.
Properly treating and labeling products that are repackaged, diluted, or
mixed with other products.
Dispensing in the proper container with the proper closure.
Informing and educating patients concerning the proper storage and use of the
products.

32. Rotation of Stock and Observance
of Expiration Dates:
• Proper rotation of stock is necessary to ensure the dispensing of
suitable products
• A product that is dispensed infrequently should be closely monitored
so that old stocks are given special attention, particularly with regard to
expiration dates.
• The manufacturer can guarantee the quality of a product up to the time
designated as its expiration date only if the product has been stored in
the original container under recommended storage conditions.

33. Storage under recommended conditions.
• These conditions are stated on the label it is
imperative to adhere to those conditions.
• They may include a specified temperature
range or a designated storage place or
condition.
(e.g., “refrigerator,” or “controlled room
temperature”) as defined in the General Notices.
• Supplemental instructions, such as a direction to protect the product
from light, also should be followed carefully.

34. • In the absence of specific instructions, the product should be
stored at controlled room temperature.
• Where a product is required to be protected from light and
is in a clear or translucent container enclosed in an
opaque outer covering, such outer covering is not to be
removed and discarded until the contents have been used.
• The product should be stored away from locations where
excessive or variable heat, cold, or light prevails, such as
those near heating pipes or fluorescent lighting.

35. CONCLUSION.
Stability testing is an essential part of the process
of ensuring that the patient receives a product
that meets established standards of safety,
efficacy and quality.

36. REFERENCE.
USP – United States
Pharmacopeia, 2008.
{1191} Stability
consideration in
dispensing practice/
General information, page
2414.

37. Thank you.