Conventional and Multivariate Statistical Methods for Evaluation of In vitro Dissolution Similarity of Bisoprolol Film-coated Tablets

In vitro dissolution testing is an important tool used for pharmaceutical development and approval of generic
medicinal product, playing a pivotal role in regulatory decision-making. This study includes evaluation and comparative analysis
of in vitro dissolution profiles of Bisoprolol film-coated tablets and in vitro dissolution profile of a reference medicinal product,
using several model-independent and model-dependent statistical methods. The evaluated medicinal product belongs to BCS
Class I (high solubility, high permeability). The similarity testing of dissolution profile is performed on the highest strength of the
dosage form, in accordance with the regulatory requirements for bioequivalence study. Obtained results have shown that in vitro
comparative dissolution analysis using pair-wise independent-model procedures, such as difference (f1) and similarity (f2) factors
are not suitable, because one of the requirements (not more than one mean value dissolves more than 85%, for any of the
formulations) was not fulfilled. Therefore, the comparison of the similarity of dissolution profiles was performed using Ratio test
methodology and multivariate model-independent approach based on generalized statistical distance (Mahalanobis distance).
Furthermore, other model-dependent approaches coupled to multivariate statistics (Weibull) were applied. The obtained results
from the performed analysis indicated a significant similarity of the compared in vitro dissolution profiles between the tested
batches from bisoprolol film-coated tablets and reference medicinal product). Implemented statistical methods can be considered
as a regulatory accepted concept for evaluation of in vitro similarity of generic medicines.