Accelerated stability studies & Expiry Date Calculation of drug substance

Accelerated stability studies & Expiry Date Calculation of drug substance

1. Accelerated stability studies & Expiry Date Calculation of drug substance

2. ACCELERATED STABILITY STUDIES : Drugs Substance are degraded by many factor like: Temperature, Light, pH, Humidity, Air etc. Due to these factors, drug substance concentration or strength is degraded during storage, shipping etc. So the drug substance stability are used to evaluate the information about drug substance stability against these factors.

3. ACCELERATED STABILITY STUDIES: Two Stability Studies: Long Term & Accelerated Stability Studies. Drug substance stability sample were taken from three successive batches. Stability samples were then kept in shelves with recommended packing material at normal storage condition for longer duration. Samples were taken to evaluate the stability profile of drug substance But these type of stability evaluation method are much time consuming and done in longer duration.

4. ACCELERATED STABILITY STUDIES: Thus to save time, drug substance are placed in stress full condition as below to evaluate the drug substance stability like Higher temperature Elevated pH Higher light intensities Because exaggerated conditions induces the drug degradation & so stability studies can be performed in short time span. Then data obtained are correlated to evaluate the drug stability at lower or normal condition from which we can derive drug retest/expiry period/date hence these studies are called “Accelerated Stability Studies”.

5. ACCELERATED STABILITY STUDIES: As per FDA guidelines, Accelerated stability studies are defined as “Studies designed to increase the rate of physical & chemical degradation of a drug substance by using exaggerated storage conditions”.

6. ACCELERATED STABILITY STUDIES: Stability Studies should include testing of those attributes of drug substances, that are susceptible to change during the storage & are likely to influence quality, safety & efficacy of drug. The Testing should cover physical, chemical, pharmacological & microbiological stabilities.

7. ACCELERATED STABILITY STUDIES: In Physical Testing, Parameters evaluated are as Colour, Odour, Particle size, Crystallization, Moisture content, Melting point etc.

8. ACCELERATED STABILITY STUDIES: In Chemical Testing, Parameters Evaluated are as Concentration of active compound Degradation Pathways & different profiles Quality Reactivity with other materials

9. ACCELERATED STABILITY STUDIES: In Microbiological Testing, Parameters Evaluated are as Degradation of drug substance due to microbial contamination In Pharmacological Testing (Mainly for drug product), Parameters Evaluated are as Change in therapeutic dose form

10. ACCELERATED STABILITY STUDIES: Accelerated Stability Studies are carried out in basic three steps Drug Substance kept at elevated stress condition i.e elevated temp., pH, Light Condition, humidity etc. Sample withdrawal at regular fixed time intervals for evaluation of recommended parameters. Evaluation of expiry / retest date / periods by establishing the relation between storage conditions and rate of degradation of drug substance.

11. ACCELERATED STABILITY STUDIES: Temp. Is the main factor which affects the drug substance stability. The most satisfactory method of influence of temp. On reaction velocity is “Arrhenius Method” Arrhenius Equation is used of accelerated stability studies of drug substance: k = A e -Ea/RT

12. ACCELERATED STABILITY STUDIES: A= Frequency Factor tells us the Frequency of collision b/w molecules drug substances at elevated temp. Ea = Activation Energy tells us the required energy to start chemical reaction In Arrhenius Equation: k = A e -Ea/RT k = Rate Constant A = Frequency Factor Ea = Activation Energy R = Gas Constant (8.314 J mole -1 K -1 ) T = Abs Temp. In Kelvin

13. ACCELERATED STABILITY STUDIES: Steps in accelerated stability studies: Samples from different batch, divided into many portions and different portions are kept under elevated temperature like 40°C, 50°C, 60°C, 70°C & so on. After each time interval, samples from different portions were withdrawn & concentration of drug substance is determines from each portions. Degradation occurs in different qty’s at different temp. At different rate.

14. ACCELERATED STABILITY STUDIES: Base on Data obtain, a graph is plotted between concentration and time as below: Time Log C 40°C 50°C 70°C 60°C

15. ACCELERATED STABILITY STUDIES: By using this graph, we can determine order of reaction & rate constant (k) at different temp. experimentally Time Log C 40°C 50°C 70°C 60°C

16. ACCELERATED STABILITY STUDIES: Collected value of k at different temp. & other corresponding data is put in Arrhenius Equation. Time Log C 40°C 50°C 70°C 60°C

17. ACCELERATED STABILITY STUDIES: k = A e -Ea/RT By taking natural logarithm of both side we get equation as: Ln k = -Ea / RT + Ln A Converting it in to Log 10 : Log k = - Ea/2.303 RT + Log A

18. ACCELERATED STABILITY STUDIES: Log k = - Ea/2.303R T + Log A Y = m x + c Where Log A= constant A graph is plotted between Log k & its corresponding reciprocal of temp (1/T). A straight line is obtained bcz above equation is similar to linear regression eq. y = mx +c.

19. ACCELERATED STABILITY STUDIES: 25°C 1/T Log k 40°C 50°C 70°C 60°C Log k at25°C

20. ACCELERATED STABILITY STUDIES: In Equation: Log k = - Ea/2.303 RT + Log A Y = m x + c Where Slope (m) = Activation Energy = Ea / 2.303 R (calculated) Higher Activation Energy = Higher Stability = More Energy Required for Reaction

21. ACCELERATED STABILITY STUDIES: Calculation of expiry date: Suppose Drug substance concentration is 100% initially and after 1 year it is 90% k = 2.303 Log C t C Where C = initial concentration = 100 % C = concentration at any time = 90 % t = time

22. ACCELERATED STABILITY STUDIES: k = 2.303 Log C t C t = 2.303 Log 100 k 90 t = 2.303 Log 1.11 k t = 2.303 X 0.045 k t = 0.104 k

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