Presentation describes on reasons to conduct stability studies, effect of physical and chemical drug decomposition, effect of light and temperature on drug decomposition and storage of drug

1. DRUG STABILITY
Prepared By
Shri. Prashant Shivgunde
Assistant Professor
Infectious Diseases Department
Maharashtra University of Health Sciences
Mumbai

2. Contents
 Introduction
 Reasons to conduct stability studies
 Types of stability
 Physical degradation
 Chemical Decomposition
 Influence of Light on drug decomposition
 Influence of Temperature on drug
decomposition
 Chemical stability testing
 Storage
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3. Introduction
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 Stability is – Time lapse during which the drug
product retains the same properties and
characteristics that it possessed at the time of
manufacture
 Expressed as Shelf Life or Expiry Period
 One of the quality attribute
 Manufacturer obliged to indicate shelf life
unless it is greater than 3 years
 No drug may be sold after 5 years

4. Reasons to conduct stability
studies
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 Product instability or Chemical degradation
may lead to Under-medication
 Drug Decomposition may convert to toxic
substance
 Instability may be due to change in physical
appearance

5. Types of Stability
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Type of Stability Conditions Maintained during the
Shelf Life of the product
Chemical Retains its chemical integrity and
labeled potency
Physical Appearance, Palatability, Uniformity,
Dissolution and Suspendability are to
be retained
Microbiological Retains sterility, effectiveness of
antimicrobial agents
Therapeutic Drug action remains unchanged
Toxicological No significant increase in toxicity

6. Physical Degradation
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 Loss of volatile Constituents
 Loss of Water
 Absorption of water
 Crystal Growth
 Polymorphism
 Color Changes

7. Chemical Decomposition
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 Hydrolysis
 Oxidation
 Optical isomerisation
 Epimerization
 Geometric isomerisation
 Polymerisation
 Absorption of carbon dioxide
 decarboxylation

8. Influence of Light on drug
decomposition
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 Light energy when strikes photolabile drugs,
activate molecules and enhance rate of
reaction.
 Decomposition due to absorption of sunlight
particularly in the spectral region of visible
blue, violet and UV wavelengths (500 to 300
nm)
 So drug decomposition testing by sunlight,
artificial light and UV rays
 Photochemical reactions usually complex,
proceed in several steps and follow zero order

9. Influence of Temperature on drug
decomposition
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 Speed of many reactions increases about two
to three times with every100 rise in temp.
 Arrhenius equation explains the effect of
reaction
k = Ae-Ea/RT
 K = specific rate constant
 A = frequency factor or Arrhenius factor
 Ea = energy of activation
 R = Ideal gas constant
 T = absolute temp.

10. Influence of Temperature on drug
decomposition
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 Energy of activation – Minimum energy that
molecule should possess so that molecular
collisions produce
 Arrhenius Factor – frequency of collisions
which can occur between molecules
A = (number of molecular collisions × probability
factor of collisions which gives reaction
product)

11. Influence of Temperature on drug
decomposition
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 Collisions theory postulates-
 Collisions must occur between molecules for the
reaction to proceed
 Reaction between molecules does not take place
unless the colliding molecules possess certain
energy
 At given temp. a fixed number of molecules
possess a certain energy

12. Influence of Temperature on drug
decomposition
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 Decomposition may sometimes increase
rather than decrease when product is stored at
low temp.
 Oxygen content enhances oxidation
 Frozen solutions cause reaction/instability to
occur if
 concentration of reactants is more in liquid phase
 Change in pH e.g. protein- change in isoelectric
point- electristatic interactions- folding/ unfolding

13. Chemical Stability Testing
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 In theory, Stability of Pharmaceutical
preparations should be evaluated by exposing
the product to normal shelf conditions for a
year or extended periods
 But not possible bcoz-
 Rate of decomposition is slow at R.T.
 Time consuming
 Uneconomical
 Practically, what is done?

14. Accelerated stability studies
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 Salient features of experimental design
 Ingredients- Consideration of different adjuvant of
drug preparation
 Decide criteria- some property of degradation like
conc. of drug/ degraded sub., color etc.
 Mechanism of chemical reaction- need not to be
explored but advantageous
 Develop assay method
 Estimate some property as function of time

15. Accelerated stability studies
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 Salient features contd.-
 Establish a linear relationship w.r.t. time,
determine order of reaction
 Selection of appropriate statistical method
 Conclusions from study should be corroborated
by results obtained at normal storage conditions
 Conduction of suitable animal experiments.

16. Accelerated stability studies
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 Method-
 Solution dosage forms are stored at elevated
temperatures, viz. 50, 60, 70, 85, 100 and 1210C
 In addition at, 400C, 75% RH and incubator temp.
(35-370C)
 Also at, R.T. (300C, 70%RH) and or refrigerator
temp. (4-50C)
 Withdraw samples during different time intervals-
 3 month interval during 1st year
 6 month interval during the 2nd and yearly thereafter

17. Accelerated stability studies
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 Drug content is estimated using stability
indicating assay method
 Plot some function of conc. Vs time, to
estimate k value at one temp.
 Similar expts. For different elevated temp. and
draw graphs as before, linear relationships are
obtained and these have different slopes,
calculate k value for each temp.

18. Accelerated stability studies
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19. Accelerated stability studies
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 Plot log k Vs reciprocal of absolute temps.
 Extrapolate straight line to R.T. or Refrigerator
temp. and read the log k (or k25) value on Y-
axis

20. Storage
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 Storing of products in well closed containers
 Storing the products by protection of light
 Storing the products in a cool place
 Storing the products by the addition of other
substances

21. Storage conditions
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 Pharmacopoeial specifications-
 Cold place: 2 to 80C
 Cool place: 8 to 250C for I.P. and 8 to150C for
USP
 Room Temperature
 Warm: 30 to 400C
 Excessive heat: Above 400C
 Controlled RT: 20 to 250C
 Freezer: -20 to -100C

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