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
1. Drug Substance kept at elevated stress condition i.e
elevated temp., pH, Light Condition, humidity etc.
2. Sample withdrawal at regular fixed time intervals
for evaluation of recommended parameters.
3. 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-1K-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
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
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
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 Log10 :
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
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 C0
t C
Where C0 = initial concentration = 100 %
C = concentration at any time = 90 %
t = time

22. ACCELERATED STABILITY STUDIES:
k = 2.303 Log C0
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