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

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.