APPROACHES ON SURROGATE METHODS FOR IN VIVO BIOEQUIVALENCE STUDY OF FORMULATED BILAYER TABLETS OF DOMPERIDONE AND ITOPRIDE

Abstract

Objective: This study aims to provide a more efficient pathway for generic drug approval while maintaining the same level of therapeutic equivalence and safety as the reference product. This was based on the equivalence of in vitro evidence other than through expensive in vivo equivalence testing. Methods: Biowaiver and IVIVC are surrogate methods for in vivo bioequivalence studies. The Biowaiver test was done according to WHO, TRS992, 2015 Annex 7, Appendix 1, the recommendation for conducting and assessing comparative dissolution. IVIVC was done by the level A Convolution method. Innovator product was used as Ganaton OD for Itopride and Motilium for Domperidone to perform the comparison testing. Results: The similarity factor (F2) between the test and innovator product of Domperidone at pH 1.2 HCl, Acetate Buffer pH 4.5, and water was 79.51, 68.00, and 58.97 and the dissimilarity factor (F1) was 7.24, 8.05 and 11.01 respectively. From the IVIVC study by level A convolution method of Cmax, AUC, Tmax of Ganaton OD and formulated Itopride were found to be 409.16ng/ml, 5652.28 ngh/ml and 4h and 252.16ng/ml, 4601.12 ngh/ml and 12 h respectively. Conclusion: The F2 limit is 50-100 and F1 is 15 mentioned as per guidelines followed for the biowaiver test, which means the formulated domperidone is deemed equivalent to (Motilium) innovator of domperidone. The predictive error on the AUC of Itopride formulated was found to be 18.59 % which was within the limit of±20 %, demonstrating the therapeutic range.