A Slope-Ratio Design for Accelerated Storage Tests

Abstract

An experimental design is presented for predicting the “expiry” dates of pharmaceutical preparations at various storage temperatures on the basis of the degradation rates observed in short time studies at elevated temperatures. The design is based on the observation that a suitable metameter of potency falls off linearly with time at a rate depending on the absolute temperature, in accordance with the Arrhenius equation. It is particularly applicable when relatively imprecise assay methods have to be employed. The design is so constructed to involve the minimum number of time-temperature combinations necessary to check the validity of the assumptions made in applying the Arrhenius equation, and also to provide a precise estimate of known error for the expiry date.