In-Vitro Dissolution Profile Comparison: Statistics and Analysis, Model Dependent Approach

Abstract

Purpose. To develop and propose a ‘model dependent’ approach for the in-vitro dissolution profiles comparison.

Methods. Diltiazem hydrochloride tablet dissolution profiles were compared using a statistical approach based on a mathematical model. A similarity region (SR) was defined based on the intra- and inter-lot parameter variances of the final production size standard lots. Statistical distances between the test and reference lot parameter means were computed and normalized. A 90% confidence region (CR) was developed around the statistical distance. The confidence region was compared with the similarity region to assess the similarity or dis-similarity of the test and reference (REF) lot dissolution profiles. Two test lots, one with a ‘minor’ modification (mm) the other with a ‘major’ modification (MM), were evaluated.

Results. ‘Weibull’ was selected as the ‘model’ function. A comparison of the confidence regions around the statistical distance of ‘mm-REF’ and ‘MM-REF’ with the similarity region, suggested that the dissolution profiles of the ‘minor’ modification lot were similar and that of ‘major’ modification lot were dis-similar to the reference lot.

Conclusions. A ‘model dependent’ approach was shown to be useful for the inter-lot in-vitro dissolution profiles comparison.