title: Statistical comparison between dissolution profiles of drug products.
abstract: The problem for assessment of similarity between dissolution profiles of two drug products is considered. The commonly used classical methods including model-dependent and model-independent approaches are reviewed. Most methods encountered the difficulties of no well-defined equivalence limits and the correlation between consecutive time points. Several methods have been proposed to account for these difficulties, e.g., the method of repeated measures (1) and the multivariate analysis approach (2). These methods, however, are sensitive to the selection of time points and complex covariance error structure. In this paper, we propose equivalence limits for similarity based on the amount of dissolved active ingredient as specified in the United States Pharmacopeia and National Formulary (USP/NF). Accordingly, we proposed a time series approach, which accounts for correlation between dissolution results at different time points. The proposed model is shown to be useful in assessment of similarity between dissolution profiles of two drug products. An example concerning dissolution testing of two lots of a drug product is used to illustrate the proposed equivalence limits and statistical methodology.
authors.affiliation: Biostatistics and Data Management, Bristol-Myers Squibb Company, Plainsboro, New Jersey 08536, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Chow
authors.forename: F Y
authors.initials: FY
authors.lastname: Ki
mesh_terms: D000704:Analysis of Variance; D002626:Chemistry, Pharmaceutical / Q000706:statistics & numerical data*; D007700:Kinetics; D010602:Pharmacopoeias as Topic; D012015:Reference Standards; D012995:Solubility; D014481:United States