Stability of Packaged Solid Dosage Forms. V. Prediction of the Effect of Aging on the Disintegration of Packaged Tablets influenced by Moisture and Heat

Abstract

The effects of moisture and temperature on tablet disintegration time were investigated on a tablet containing gelatin as a binder under accelerated conditions. The higher the ambient temperature was and the more moisture the tablet contained during storage, the longer the disintegration time became. Among several kinetic models investigated, a half-order reaction model was found to be most suitable, when the ratio of the disintegration time of the aged samples to that of the initial ones was taken as a variable to be predicted. The effects of moisture and heat on the disintegration time ratio were analyzed by a multiple regression technique on the basis of the Carstensen equation. In order to estimate the effect of aging on the disintegration time ratio, tablets in several kinds of moisture-semipermeable packages, including an overwrapped package, were examined in artificial climate laboratories. The effect of aging could be predicted by an iterative calculation through a mathematical model in which the kinetics of the increase in the disintegration time ratio was combined with the moisture permeabilities of the packages. It was found that the simulated values could represent the observed data fairly well, though the confidence intervals of the predicted values were rather wide owing to the variances of the experimental data obtained.