The document discusses accelerated stability testing which uses exaggerated storage conditions to rapidly assess a drug product's stability over time. It describes the Arrhenius equation which relates reaction rate to temperature and activation energy. Common accelerated tests involve storing samples at elevated temperatures, humidity, oxygen, or light levels. While useful, accelerated testing has limitations when degradation depends on other factors like microbes or diffusion. ICH guidelines provide standard methods for stability testing and data analysis.

1. ACCELERATED STABILITY
STUDY
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2. CONTENTS
 Introduction
 Activation energy
 Arrhenius equation
 Accelerated stability testing
 Limitations of accelerated stability testing
 ICH guidelines
 References
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3. INTRODUCTION
 Stability:
Stability of pharmaceutical product may be
defined as the capability of a particular
formulation in a specific container/closure
system to remain within its physical, chemical,
microbiological, therapeutic and toxicological
specification.
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4. Need for stability testing:
1. Provide evidence as to how the quality of the drug
product varies with time.
2. Establish shelf life for the drug product.
3. Determine recommended storage conditions.
4. Determine container closure system suitability.
5. Safety point of view of patient.
6. Prevention of economical repercussion.
7. Essential quality attribute.
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5. ACCORDING TO USP TYPES OF
STABILITY
Type Condition to be
maintained
1.Chemical : Chemical integrity &
lebelled potency
2.Physical: Appearance, palatability,
uniformality.
3.Microbiological Sterility
4.Therapeutic: Drug action remains
unchanged
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5.Toxicological: No increase in toxicity

6. ACTIVATION ENERGY:
It is defined as the energy that must be overcome in order for a
chemical reaction to occur. Activation energy may also be defined
as the minimum energy required to start a chemical reaction.
The activation energy of a reaction is usually denoted by Ea, and
given in units of kilojoules per mole.
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7. ARRHENIUS EQUATION :
Arrhenius equation gives "the dependence of the rate constant
k of chemical reaction on the temperature T (in absolute
temperature, such as Kelvin or degrees Rankine) and activation
energy Ea", as shown below:
(1)
Where k=specific rate constant
A=frequency factor
Ea= activation energy
R=ideal gas constant
T=absolute temperature
Take log on both sides,
ln k = ln A –Ea/RT ln e (2)
Converting eq. 2 to log 10
log k = log A – Ea/2.303RT 7

8. Estimation of k:
1.Reaction is conducted at several temp.
2.Conc. is determined at different time period.
3.Order of reaction is identified.
4.From slope of line k is calculated.
Fig. Estimation
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9. ESTIMATION OF ACTIVATION ENERGY:
 A graph can be drawn by taking log k on y-axis and
reciprocal temperature (1/T) on x-axis.
 A straight line is obtained, the slope of the line is
negative and the magnitude is Ea /2.303 R.
 The intercept corresponds to log A.
 All the constants in the Arrhenius equation can be
obtained from the graph.
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Fig. estimation of activation energy

10. Calculation of shelf life:
ORDER X axis Y axis HALF LIFE SHELF LIFE
ZERO Time (a-x) a/2k 0.1A0/K0
FIRST Time log(a-x) 0.693/k 0.105/K1
SECOND Time 1/(a-x) 1/ka -
(a=b)
SECOND Time Log b(a-x)/a 1/ka -
(a≠b) (b-x)
THIRD Time 1/(a-x)2 3/2ka2 -

11. TYPES OF STABILITY TESTS:
 Long term stability tests
 Field test
 Accelerated stability tests
Accelerated stability studies:
Studies designed to increase the rate of chemical
degradation or physical change of an active
substance or drug product by using exaggerated
storage conditions as part of the formal, definitive
storage programme.
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12. TESTS AT ELEVATED TEMPERATURE:
 Drug liquid preparation stored at 50, 60, 70,85,100
and 121˚c.
 Also study performed at R.T. and or refrigerator
temp.
 Sampling:
First year- 3 month interval
Second year- 6 month interval
 Four climatic zones:
Temperate zone 21˚c/45%RH
Mediterranean zone 25˚c/60%RH
Tropical zone 30˚c/70%RH
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Desert zone 30˚c/35%RH

13. TESTS AT HIGH INTENSITY OF LIGHT:
 Drug substances fade or darken on exposing to light, can be
controlled by using amber glass or opaque container.
 By exposing drug substance to 400 & 900 (FC)of illumination for 4 &
2 weeks to light and another sample examined protected from light .
 Results found on appearance and chemical loss may be recorded.
 Comparing color or using diffused reflectance spectroscopy for
examination.
 e.g. cycloprofen becomes very yellow after five days under 900 foot
candles of light.
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14. TESTS AT HIGH PARTIAL PRESSURE OF OXYGEN:
 Sensitivity of the drugs to atmospheric oxygen must
be evaluated from which it should be packed in
inert atmospheric condition with antioxidants is
decided .
 Here, high oxygen tension plays important role to
investigate stability Usually ,40% of oxygen
atmosphere allows for rapid evaluation.
 Results were correlated with inert & without inert
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condition .

15. TESTS AT HIGH RELATIVE HUMIDITY:
 Presence of moisture may cause hydrolysis and
oxidation.
 These reactions may accelerated by exposing the
drug to different relative humidities.
 Control humidity by Lab desiccators
 Closed dessicator are placed in an oven to provide
constant temperature.
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16. LIMITATIONS OF ACCELERATED
STABILITY TESTING
 Valid only when the break down depends on
temperature.
 The energy of activation obtained in the study
should be between 10 to 30 kcal/mole.
 It is not useful when degradation is due to:
• Microbial contamination
• Photochemical reactions
• Diffusion
• Excessive agitation
 When the product looses its physical integrity at
higher temperatures.
 When the order changes at elevated temperatures.
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17. STABILITY PROTOCOL:
 Containers and closures
 Container orientation
 Sampling interval
 Type, size and number of batches
 Plan of sampling
 Storage conditions
 Test methodology
 Acceptance criteria
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18. ICH GUIDELINES ON STRESS
TESTING:
Standard Title and reference
ICH Q1A(R2) Stability Testing of New Drug Substances
and Products (the parent guideline)
ICH Q1B Photostability Testing of New Drug
Substances and Products
ICH Q C Stability testing of new dosage forms
ICH D Bracketing and matrixing designs
ICH Q E Evaluation of stability data
ICH Q F Stability data package for registration 18
applications in climatic zone I and IV

19. REFERENCES
 Patrick J.Sinko , Martin’s Physical Pharmacy and
Pharmaceutical Sciences.
 Theory and practice of Industrial Pharmacy –
Lachman
 International Stability Testing Drug stability-
Cartensen
 C.V.S. Subrahmanyam
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 www.ich.org

20. THANK YOU…
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