Accelerated stability testing are studies designed to increase the rate of chemical degradation and physical change of a
drug by using exaggerated storage conditions as part of the formal stability testing programme. The data thus obtained, in addition to those derived from real-time
stability studies, may be used to assess longer-term chemical effects under nonaccelerated conditions and to evaluate the impact of short-term excursions outside the label storage conditions, as might occur during shipping. The results of accelerated
testing studies are not always predictive of physical changes.
In the olden days, before a drug product is marketed, it has been the practice to evaluate its stability by placing it on storage test which involves examining the product for quality and potency at suitable time intervals corresponding to the normal period the product is likely to be used. Since this period can be as long as 2-5 years, this type of testing is time-consuming and expensive.
Therefore it has become necessary to device a technique for rapid or accelerated testing during the period of product development stages that will enable fairly accurate prediction of the drug’s long term stability. A prediction of the life of the product may be made by accelerating the decomposition process and extrapolating the results to normal storage conditions. It must be noted that accelerated stability tests are not expected to replace statutory stability testing programme for the product finally marketed.
When determining the chemical stability of a pharmaceutical product, it is essential that the assay method employed should be sufficiently specific to distinguish between the parent drug and its decomposition products. If there are many toxic decomposition products, analysis can be restricted to assays for the most toxic product and for the undecomposed parent drugs.
Acceleration of chemical decomposition is achieved by raising the temperature of the
preparations. Application of the principles of chemical kinetics to the results of accelerated storage tests carried out at three or more elevated temperatures enables the prediction of the effective shelf-life of the preparation at normal temperatures.
The order of reaction for the decomposition process is determined by plotting the
appropriate function of concentration against time and obtaining a linear relationship. The decomposition at each of the elevated temperatures can be calculated from the slope of the line. The Arrhenius relationship (see equation) is then employed to determine the reaction velocity constant for the decomposition at room temperature (see Fig 2).
Objectives of Accelerated Stability Tests
The objective of accelerated stability tests may include the following:
- Rapid detection of deterioration in different initial formulations of the same product; this is of benefit in selecting the best formulation from a series of possible choices.
- Prediction of shelf-life which is the time from manufacture when a product will remain satisfactory when stored under expected or directed storage conditions; and
- Provision of a rapid means of quality control, which ensures that no unexpected change has occurred in the stored product.
Depending on the chosen objective; for example, if the 1st objective is selected, the best formulation from a series of possible formulations is the one that exhibit the least amount of decomposition in a given time under the influence of a reasonably high storage temperatures e.g. 37, 52 and 76°C (see diagrams). The results of such a test are shown below: (Fig 1)
The second objective is achieved by using the results obtained from an accelerated stability test to predict the amount of decomposition in a product after a longer period of storage under normal conditions. This is illustrated in Fig. 3.
In fig. 3 the amount of decomposition X
obtained after the short time, t1 is used to
predict the value of Y after time, t2.
The use of accelerated tests in achieving
the third objective is shown in Fig 4
which illustrates that a single measurement taken after a given time t should fall below an acceptable limit of decomposition for a product subjected to the challenge involved in the test.
