Conventional and Multivariate Statistical Methods for Evaluation of In vitro Dissolution Similarity of Bisoprolol Film-coated Tablets
International Journal of Pharmacy and Chemistry
Volume 6, Issue 2, March 2020, Pages: 16-25
Received: Jun. 9, 2020;
Accepted: Jun. 20, 2020;
Published: Jul. 4, 2020
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Ivana Mitrevska, Research & Development, Alkaloid AD, Skopje, R. North Macedonia
Ljupco Pejov, Department of Chemistry, Bioscience and Environmental Engineering, Faculty of Science and Technology, University of Stavanger, Stavanger, Norway; Institute of Chemistry, ‘Ss. Cyril and Methodius” University, Faculty of Natural Sciences and Mathematics, Skopje, R. North Macedonia
Marija Jovanovska, Research & Development, Alkaloid AD, Skopje, R. North Macedonia
Suzan Memed-Sejfulah, Research & Development, Alkaloid AD, Skopje, R. North Macedonia
Katerina Brezovska, Institute of Applied Chemistry and Pharmaceutical Analysis, ‘Ss. Cyril and Methodius” University, Faculty of Pharmacy, Skopje, R. North Macedonia
Aneta Dimitrovska, Institute of Applied Chemistry and Pharmaceutical Analysis, ‘Ss. Cyril and Methodius” University, Faculty of Pharmacy, Skopje, R. North Macedonia
Sonja Ugarkovic, Research & Development, Alkaloid AD, Skopje, R. North Macedonia
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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.
Generic Medicinal Product, In vitro Dissolution Similarity, Model-dependent Methods, Model-independent Methods, Bisoprolol Film-coated Tablets
To cite this article
Conventional and Multivariate Statistical Methods for Evaluation of In vitro Dissolution Similarity of Bisoprolol Film-coated Tablets, International Journal of Pharmacy and Chemistry.
Vol. 6, No. 2,
2020, pp. 16-25.
Copyright © 2020 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/
) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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