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Accelerated Stability Testing

Accelerated stability testing uses the Arrhenius equation to relate the degradation rate of pharmaceutical products to temperature. Higher temperatures are used to accelerate degradation, and the results are extrapolated to predict shelf life at room temperature. The procedure involves storing products at different temperatures, assaying samples over time to determine drug concentration remaining, calculating rate constants at each temperature, plotting an Arrhenius graph to extrapolate the rate constant at room temperature, and using this to calculate shelf life.

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Kevin Garala
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399 views

Accelerated Stability Testing

Accelerated stability testing uses the Arrhenius equation to relate the degradation rate of pharmaceutical products to temperature. Higher temperatures are used to accelerate degradation, and the results are extrapolated to predict shelf life at room temperature. The procedure involves storing products at different temperatures, assaying samples over time to determine drug concentration remaining, calculating rate constants at each temperature, plotting an Arrhenius graph to extrapolate the rate constant at room temperature, and using this to calculate shelf life.

Uploaded by

Kevin Garala
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as DOCX, PDF, TXT or read online on Scribd
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Accelerated Stability Testing

Aim: To determine the shelf life of the given product by accelerated stability
testing.

Principle: The time taken for 10 % of the drug in the product to decompose is
called shelf life or t90. Shelf life of a product can be determined quickly by
accelerated stability testing.

The principle involved in accelerated stability testing method is the Arrhenius


relationship between temperature and rate of a reaction. According to
Arrhenius, the rate of a reaction increases with rise in temperature. The
Arrhenius equation is given below.

K=Ae - Ea /RT
----- 1, log K = log A – Ea /2.303 RT --- 2

K = Rate constant for the degradation of Ea = Energy of activation


drug.

A = Arrhenius factor or frequency factor T = Absolute temperature

When the pharmaceutical product is exposed to extreme conditions like high


temperature, high humidity, centrifugation etc, the degradation of drug
product is accelerated. The results obtained at extreme conditions are extended
to room temperature to predict the shelf life of the product.

Procedure:

1. Store the pharmaceutical product at different higher temperatures.


2. Assay the pharmaceutical product at different time intervals to determine
the amount of drug remaining in the product.
3. Determine the order of degradation of drug by graphical method.
4. From the graph, find out the rate constant for degradation of drug at
different temperatures.
5. Construct an Arrhenius plot i.e. log K Vs 1/T and extrapolate the resulting
straight line to room temperature. From this graph, find out the rate constant
for degradation of drug at room temperature (25 oC).
6. Substitute K25 in the suitable zero or first order rate equation to determine
the shelf life of the product.

Procedure for short cut method:

1. Store the pharmaceutical product at different higher temperatures.


2. Assay the pharmaceutical product at different time intervals to determine
the amount of drug remaining in the product.
3. From the graphical plots find out the shelf life at different temperatures.
4. Construct an Arrhenius plot of log t90 Vs 1/T, and to determine shelf life
extrapolate the straight line to room temperature (25 oC).

Report:

1. The drug is degrading according to ___________ order kinetics.


2. The shelf life of the product is _____________ from the date of manufacture.
3. From short cut method the shelf life of the product is found to be _______.

Problem 1: A liquid oral of drug ‘x’ was stored at 43.3, 51.5 and 71.67 oC. It
was analyzed at frequent intervals to determine the % of drug remaining and
the results are given in the below table. The product becomes ineffective when
20% of the drug gets degraded. Determine the shelf life of the product by
accelerated stability testing method.

S.N
Temperature, oC % of drug remaining after time in months
O
0 1 2 3 4 6 10
1 43.30 100 ---- 79.43 ---- 63.1 ---- 31.62
2 51.50 100 ---- 66.06 ---- 44.66 29.51 13.18
3 71.67 100 54.95 30.19 16.59 9.25 ---- ----

Observations and Calculations:

S.N
Temperature, oC Log (% of drug remaining) after time in months
O
0 1 2 3 4 6 10
1 43.3 ---- ---- ----
2 51.5 ---- ----
3 71.67 ---- ----

S.NO o
C T 1 / T X 10 5
Log K t80 log t80
1 43.30
2 51.50
3 71.67
4 25.00

Ans:K43.3 = 0.115/month K51.5 = 0.202/month


K71.67 = 0.556/month t80 = 6.34 months
Accelerated stability testing
• The concept of accelerated stability testing is based upon the Arrhenius
equation

Where,
K = degradation rate/s,
A = frequency factor/s, (Specifically relates to molecular collision, deals with
the frequency of molecules that collide in the correct orientation and with
enough energy to initiate a reaction. It is a factor that is determined
experimentally, as it varies with different reactions)
ΔE = activation energy (kJ/mol),
R = universal gas constant (0.00831kJ/mol),
T=absolute temperature (K)

This equation describes the relationship between storage temperatures and


degradation rate. Using Arrhenius equation, projection of stability from the
degradation rates observed at high temperatures for some degradation
processes can be determined.

• When the activation energy is known, the degradation rate at low


temperatures may be projected from those observed at “stress” temperatures

• The stress tests used in the current International Conference on


Harmonization (ICH) guideline (e.g., 40% for products to be stored at
controlled room temperature) were developed from a model that assumes
energy of activation of about 83 kJ per mole.
• It explains the effect of temperature on rate of a reaction. According to
Arrhenius, for every 10º rise in temperature, the speed of reaction increases
about 2-3 times
• Estimation of k value
• The reaction is conducted at several temperatures.
• Concentration of reactants is determined (log(a-x).
• Appropriate graphs are drawn for the kinetic data.
• Data is processed for all the orders.
• The order of the reaction is identified.
• From the slopes of the lines, k values are calculated for all temperatures.
By using Arrhenius relationship, Log k values are plotted against reciprocal of
absolute temperature Extrapolate the straight line to room temperature (k25)
and read the log k value on y-axis

• With substitution of the k25 value in the equation, the shelf life of the
product is calculated:

• Shelf life is defined as the time necessary for the drug to decay to 90% of its
original concentration.

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