on storage for a specified time. In order to make such an assurance, we obviously need to conduct a rigorous stability testing programme on the product in the form that is finally to be marketed. Since the testing period can be as long as two years, it has become essential to devise a more rapid technique which can be used during product development to speed up the identification of the most suitable formulation. In this section we shall examine ways of predicting the chemical stability of a formulation during preformu-lation studies using accelerated storage tests. We will not be considering the toxicological or microbiological studies or the determination of physical stability, all of which are essential elements in the overall stability testing of the formulation but which are outside the scope of this chapter. Although most of this section will be concerned with the prediction of the effect of temperature on drug decomposition, other environmental factors will also be briefly considered.

4.5.1 Effect of temperature on stability

We have already considered the basic method of accelerating the chemical decomposition by raising the temperature of the preparations. We will briefly reconsider essential steps in the process. The order of reaction can be determined by plotting stability data at several elevated temperatures according to the equations relating decomposition to time for each of the orders of reaction, until linear plots are obtained. We can now calculate values of rate constant at each temperature from the gradient of these plots, and plot the logarithm of k against reciprocal temperature according to the Arrhenius equation:

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