The effect of the composition of a fixed dose combination on bioequivalence results

Publication date: 30 July 2018 Source:International Journal of Pharmaceutics, Volume 546, Issues 1–2 Author(s): Jana Šalandová, Aleš Franc, Jiří Hofmann, Aleksandra Dumicic, Lenka Kukačková, Tereza Červená, Josef Beránek, Jan Srbek, Andrej Repický, Beata Vladovičová, David Vetchý The purpose of this work was to develop a new supergeneric product Meloxicam/Omeprazole. Such a combination brings a benefit in terms of decreasing side effects for the patients using meloxicam. The new combination is composed of a meloxicam powder blend (MPB) and omeprazole gastro-resistant pellets (OAP) in hard gelatin capsules. The main tasks were to select the excipients to keep the functional layer of OAP active and to prove the bioequivalence to the original products of meloxicam tablets together with omeprazole capsules. Although dissolution profiles similar to the original product were obtained, the unexpected results of omeprazole low bioavailability in the fed bioequivalence study (BES I) showed the necessity to investigate the formulation in greater depth. A modified more complex dissolution method was developed in order to understand the release of omeprazole under gastric conditions. This method revealed the degradation of omeprazole in the formulation when exposed to the fed conditions because of the increase in microenvironmental pH in the capsule caused by trisodium citrate, commonly used for improving solubility of meloxicam. This pH increase dissolved th...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research