Investigation of the Stability with Bracketing Design in Tablet Form

Abstract

EMA, FDA and ICH guidelines provide guidance to manufacturers of pharmaceutical products for planning and evaluating the stability tests. A full study design is discribed as a model in which samples for every combination of all design factors are tested at all time points. On the other hand matrix and bracket desings are known as a reduced design which can be a suitable alternative to a full design when certain design factors are involved. The bracketing design assumes that the stability of any intermediate levels is represented by the stability of the extremes tested. Reducing number of stability test with bracketing design is considered as an alternative to the full factorial design to avoid costly and time consuming. In this study, an application of the survey of 4 different forms of glimepiride tablet by bracket design method is given. Among the four doses of the medicine, the extreme amounts of active pharmaceutical ingredient are chosen and several quality parameters such as content uniformity, weight variation, tablet crushing strength, disintegration and friability, tablet dissolution rate, disintegration time, active substance ingredient amount, diameter and thickness of tablets are determined in accelerated and long-term stability conditions. Using these results, the properties of tablets with intermediate amounts are calculated with the help of statistical modeling. For four of six examined quality control parameters the r² values are close to 1 and all found F values are greater than the tabulated values. These results show that the correlations used in the modeling part are accurate.