Adjusting dissolution specifications for the variability induced by storage conditions

The United States Pharmacopeia requires that drug products meet established dissolution specifications throughout their shelf life. Whereas chemical stability for six months at accelerated storage conditions is generally regarded as providing a two-year expiry period, stress conditions are not considered predictive of dissolution stability at controlled room temperature. This paper presents an application of response surface methodology intended to incorporate the variability induced by storage temperature and relative humidity into robust product dissolution specifications. Contour plots, depicting one-sided tolerance limits of percent released, are presented as a function of crushing strength and dissolution time.