Stability of Packaged Solid Dosage Forms. VI. Shelf-life Prediction of Packaged Prednisolone Tablets in Relation to Dissolution Properties

Abstract

The shelf lives of prednisolone tablets in a moisture-semipermeable package and a glass bottle were examined in relation to the in vitro dissolution rate. The effects of moisture and heat on the tablet dissolution rates, which were obtained by use of the Kitazawa equation, were investigated under various temperature-humidity conditions. Retardation of the dissolution rate was found to be caused by increasing moisture content at ambient temperature. The dependence of the reduction in the dissolution rate on moisture and heat was analyzed by a multiple regression technique on the basis of the Carstensen equation. Predictions of the reduction in the dissolution rates for packaged tablets kept under various conditions were performed by an iterative calculation over a time interval through a mathematical model which combined the multiple regression function with the moisture permeabilities of the packages. There were good agreements between the predicted values and the observed data. The prediction procedure utilizing the rate constants together with their confidence limits gave reliable estimates of the shelf lives of the packaged tablets.