The accelerated Stability Study method is designed to predict stability and hence the shelf life of products under normal or recommended storage conditions by different guidelines for carrying out the study under accelerated conditions of temperature, moisture, and light.
As can say an accelerated stability study is used to determine the shelf life and potential degradation of a drug product under different environmental conditions. Accelerated stability studies are typically conducted by storing the drug product at higher temperatures and/or humidities than would be encountered under normal storage conditions. The drug product is then analyzed at predetermined intervals to examine any changes in its physical, chemical, and/or biological properties. The results of the accelerated stability study are used to establish expiration dates and storage conditions for that product.
It is important to note that the results of an accelerated stability study may not accurately predict the long-term stability of a drug product under real-world storage conditions. Therefore, it is typically recommended to confirm the results of an accelerated stability study with a separate long-term stability study under actual storage conditions.
ICH and WHO guidelines on stability studies
The International Council for Harmonisation (ICH) Requirements for Pharmaceuticals for Human Use and the World Health Organization (WHO) are both international organizations that have designed their own guidelines and recommendations for the development, registration, and regulatory approval of pharmaceutical products. Both organizations have published guidelines on stability studies to provide guidance on the conduct and evaluation of stability studies for pharmaceutical products.
The ICH has published a number of guidelines on stability studies, including the following:
|ICH Q1A (R2)||Stability Testing of New Drug Substances and Products|
|ICH Q1B||Photostability Testing of New Drug Substances and Products:|
|ICH Q1C||Stability Testing for New Dosage Form|
|ICH Q1D||Bracketing and matrixing designs for stability testing of drug substances and products|
|ICH Q1E||Evaluation of stability data|
|ICH Q1F||Stability data for climate zone III and zone IV|
The WHO has also published guidelines on stability studies, including the following:
WHO Technical Report Series, No. 961: Stability Testing of API drugs and Finished Pharmaceutical Products
WHO Technical Report Series, No. 963: Stability Testing of Herbal Medicinal Products:
Both the ICH and WHO guidelines on stability studies provide recommendations on the design and execution of stability studies, as well as the data that should be generated and reported. These guidelines are intended to help ensure the quality, safety, and efficacy of pharmaceutical products and to facilitate the regulatory approval process.
The Different Climate Zone
|Climate Zone Types||Conditions|
|Zone I||Moderate/ temperature climate (21°C at 45% RH)|
|Zone II||Subtropical climate (25°C at 60% RH)|
|Zone III||Hot/ Dry climate (30°C at 35% RH)|
|Zone IV||Hot/Humid climate (30°C at 70% RH)|
|Zone I||Russia, Canada, Great Britain, and North Europe|
|Zone II||USA, Japan, and South Europe|
|Zone III||Iran, Iraq, and Sudan|
|Zone IV||Indonesia, Ghana, Brazil, and the Philippines|
The objective of the Accelerated Stability Study
- The objective of an accelerated stability study is to determine the effect of environmental factors (such as temperature, humidity, and light) on the stability of a product. The study is conducted by exposing the product to extreme conditions that are likely to accelerate the rate of degradation or change in the product and then comparing the results to those obtained from testing the product under normal storage conditions.
- The purpose of an accelerated stability study is to estimate the shelf life of a product, which is the length of time that a product can be stored and still meet its intended quality, purity, and potency standards. This information is important for ensuring the safety and effectiveness of the product, as well as for planning and implementing appropriate storage, handling, and distribution processes.
- Accelerated stability studies are often conducted in conjunction with real-time stability studies, which involve storing the product under normal conditions and periodically testing it to monitor its stability over time. The results of both types of studies are used to develop a stability-indicating assay, which is a test that can be used to determine the stability of the product during storage and use.
Time/Storage Condition for a stability study
|Types of Stability testing||Condition|
|Accelerated Stability study||Duration- 6 Months|
Temp.: 40 ± 2°C
RH: 75± 5%
|Intermediate Stability study||Duration- 6 Months|
Temp.: 30 ± 2°C
RH: 65± 5%
|Long-term Stability study||Duration- 5 Years|
Temp.: 25 ± 2°C
RH: 60± 5%
Prediction of self -Life equation
Arrhenius’s equation explains the effect of temperature on the rate of reaction. according to Arrhenius equation for every 10°C rise, the speed of reaction is about 2 to 3 times.
Log K= LogA-Ea/2.303RT
Steps involve in Accelerated stability study/Testing
- The preparation is stored at different elevated temperatures likes (40, 50, 60, and 70°C)
- the concentration of a reactant at each elevated temperature is also determined.
- Samples are withdrawn at different time intervals
- The rate of reaction is determined by plotting the concentration against time and a linear relationship is determined.
- The straight line in a graph permits the estimation of the k value from the slope, from the slope of the line reaction rate constant k for degradation at each elevation temperature is calculated.
- The reaction rate constant k for degradation of room temperature that is 25°C is determined.
- The k value obtained for 25°C is substituted in the already determined order of reaction and an estimate is obtained for the self-life of the product.
Limitation of accelerated stability analysis:
- Stability prediction based on the Arrhenius equation is valid only when the energy of activation for thermal decomposition lies between 10 to 30 kcal/mole
- This method is not used in the case of complex reactions because the Arrhenius equation consists of only one rate constant.
- This method is not applicable if degradation is due to freezing, microbial contamination, or excess agitation.
- A product that loose its physical integrity at elevated temperature is not suitable for this method.
- It is not valid when the order changes at a higher temperature.