This document provides an overview of stability studies, including the basic concepts, objectives, factors affecting stability, types of stability studies, ICH guidelines, climatic zones, steps for stability testing, and a reference. It defines stability as a drug substance or product retaining its properties and characteristics within specifications for a given time period. The objectives of stability testing are to determine shelf life and storage conditions, ensure formulation and packaging adequacy, understand quality variations over time, and prevent recalls. ICH guidelines cover testing requirements. Studies include long-term, accelerated, and intermediate testing under various climatic zone storage conditions.

1. Seminar on
Basic concept and objective of
Stability studies
PRESENTED BY:
Sachin. S .Bhagat
M.pharm (pharmaceutics)
Roll no :13
GUIDED BY-
Dr.D.V Derle
(principal)
MVP Samaj’s College Of Pharmacy, Nashik.
.

2. Contents.
• Introduction
• Factors affecting stability
• Types of stability
• Objective of stability
• Types of stability study
• ICH Guideline of stability study
• Climatic zone
• Steps of stability testing
• Reference

3. Introduction :
• Drug stability refers to capacity of drug substance or product to
remain within specification of identity, strength, quality and purity in
specific period of time
• Stability is officially define as time lapse during which the drug
product retain the same properties and characteristics that it
possessed at time of manufacture
• The stability of a product is expressed as the expiry period or
technically as shelf life

4. Shelf life.
• It is defined as the time required for the concentration of
drug/reactant to reduced to 90% of its initial concentration
• It represent as t90
• Unit : time/sec
• Formula : t90 =(a-0.9a)/k0
Where , a= initial concentration
k= specific rate constant for zero order reaction

5. Factors affecting Drug stability:
Primary factors:
• pH
• Temperature
• Moisture
• Humidity
• Light
• Container and closure
• Storage

6. Secondary factors:
• Particle size (suspension and emulsion)
• Molecular binding
• Diffusion of drug and excipient

7. Types of stability
• Therapeutical stability : therapeutic activity must be unchanged
• Chemical stability : chemical must be in pure form
• Microbiological stability : resistance to microbial growth
• Toxicological stability : no significant change
• Physical stability :appearance, palatability ,uniformity & suspend
ability

8. what happen due to instability:
1)increase in concentration of API:
for some product ,loss of vehicle can result in an increase in
concentration of active drug.
e.g. : lidocaine gel - perfusion bag sometime allow solvant to
evaporate so product within bag show an increase in concentration.
2)loss of content uniformity :
Suspension are the drug delivery system most likely to show content
uniformity as a function of time and for stability of such product
sedimentation volume and ease of redispersion should determine .
3)decline microbiological status :
Microbiological status of pharmaceutical can decline with time
prevention: drug assay for bioburden at time of manufacture, within
limit, and when tested after say 6 month storage exceed the maximum
permitted limits

9. 4) formation of toxic degradation product :
If drug degrade to molecular species that is toxic ,there must be special attention
given to the quantity of such product e.g conversion of p-amino salicylic acid to
p- amino phenol
Objective of stability testing :
1)concern for patient welfare :
primary reason for stability testing should be our concern for the well-being of
patient who will use our product
2) To protect the reputation of the producer:
The most important reason for conducting a stability testing program is to
assure ourselves the our product will indeed retain fitness for the use with respect
to all functionally relevant for along as they are on the market

10. 3)To check shelf life & storage condition & labelling specification :
By carrying out stability testing we can find out the shelf life and expiry
date. We can have information of best storage condition at which drug will
contain its stability for long time
If their is specification we can write on label
4) Adequate formulation &container closure system:
We can have idea about the formulation which will be more stable .and if during
stability testing we find any specification of container
E.g : menadione injection packed in amber color ampoule to protect from photo
degradation
5)How quality of drug substance or product varies with time under
influence of various factor
6) degradation of product& and possible degradation pathway

11. 7) Prevent great loss by recalling the batch due to stability
8)loss and increase in concentration of API
9) providing evidence on how quality of drug substance or product
varies with time under the influence of various factors like temperature,
humidity and light
10) loss of pharmaceutical elegance and patient acceptability

12. Guidance and requirement for stability study covered in :
1) international conference on harmonization (ICH)
2) WHO guideline for stability testing
3) US-FDA guideline
4) SUPAC guideline scale-up and post approval changes

13. Types of stability studies :
1) accelerated stability testing
2) intermediate stability testing
3) long term testing
4)degradation testing
5) photo stability testing

14. ICH guideline for stability testing :
ICH GUIDELINE TITLE
Q1A Stability testing of new drug product and substance
Q1B
Stability testing : photo stability testing of new drug product and
substance
Q1C Stability testing for new dosage form
Q1D
Bracketing and matrixing designs for stability testing of drug
substance and product
Q1E Evaluation of stability data
Q1F
Stability data package for registration application in climatic zone III
and IV

15. Climatic zones :
ZONES CLIMATE Storage condition
ZONE I Temperate 21 C/45% RH
ZONE II
Subtropical and high
humid
25 C/60%RH
ZONE III Hot & dry 30 C/35%RH
ZONE IV Hot & humid 30C/70%RH

16. Steps of stability testing :
1) selection of batches
2) Testing frequency
3) Storage condition
4) Acceptance criteria
5) Evaluation
6) Labelling

17. SELECTION OF BATCHES:
1)Stability information from accelerated & long term stability should provided on batches
Of same formulation & dosage form in container and closure purpose of manufacture
2)stability data of 3 primary batches should provided
3) expected that at least first 2 batches of manufacture should be tested for long term stab
4)the composition ,batch size, batch no & manufacturing date should documented

18. TESTING FREQUENCY:
According to ICH
Stability testing Testing interval
Real time testing (Q1) 0,3,6,9,12,24 Month
Accelerated testing 0,3& 6 month
Intermediate 0,6,9& 12 month
• For accelerated testing ,FDA suggest : 0,2,4& 6month
WHO suggest :0,1,2,3&6 month
• FDA & WHO do not suggest for intermediate testing

19. Storage condition :
According to Q1A &Q1F
ZONE I &II Temperature RELATIVE HUMDITY Time
Long term study 25℃ +2 60% + 5 12 month
Intermediate study 30℃ + 2 65% + 5 6 month
Accelerated study 40℃+ 2 75% + 5 6 month
ZONE III &IV Temperature Relative humidity
Long term 30℃+2 65% +5
Accelerated 40℃+2 75% +5

20. Acceptance criteria :
Significant change for a drug substance is defined as failure to
meet its specification
1) A 5% potency loss from initial assay value of a batch
2) Any specified degrading exceeding its specification limit
3) The product exceeding the pH limit
4) Dissolution exceeding specification limit for 12 capsule or
tablet
5) Failure to meet specification for appearance and physical
properties (e.g , color ,phase separation , caking, hardness,
resuspendability
6) 5% loss in water from its initial value form packaged in semi
permeable container

21. Evaluation
1) tabulate and plot stability data on all attributes at all storage condition and
evaluate each attribute separately
2) No significant change at accelerated condition within six month
3) Long term data show little or no variability and little or no change over time

22. Labelling :
1)Use of term such as “ ambient condition ’ or “ room temperature” is
unacceptable
2) where applicable , specific requirement should be stated e.g.
“protect from sunlight” ,”protection from freezing” the use of
precautionary statement should not be substituted
3)normal storage condition have been defined by WHO as “store in dry
, well ventilated premises at temperature of 15 - 25 ℃ .
4) store in refrigeration , no freezing ( 2& 8 )
5) in deep freezer (-18. )
6) In freezer (-5 to 20 )

23. REERENCE :
1) Drug stability : principles and practices ,1st Edition, edited by Jens T.
Carstensen and C.T. Rhodes (Marcel Dekker Inc, New York ,1990)
2) Textbook of physical pharmacy by C.V.S Subrahmanyam published by
M.K jain for Vallabh prakashan 5th edition 2004
3)
http://pharmaquest.weebly.com/uploads/9/9/4/2/9942916/basic_concept
_of_stability_studies.pdf