Development of a drug release methodology for carbamazepine CR tablets based on bioequivalence evaluation

The aim of this study was to investigate the influence of experimental conditions on carbamazepine (CBZ) release from the two controlled-release (CR) tablet formulations with proven bioequivalence and to propose the universal release method which would be biorelevant. In vitro data were obtained in various release media using the USP apparatus II in order to assess their influence on CBZ release from CR tablets. An empirical correlation between in vivo plasma concentration data expressed as a fraction drug absorbed and the cumulative amount of in vitro release was established. The most complete release and highest level A correlation was observed by using the half change method (HCM) compared to other release methodologies tested. The results obtained indicate that the release test developed offers a promising in vitro tool for predicting the in vivo performance of CBZ CR tablets, ensuring batch to batch bioequivalence and verification of certain postapproval changes without the need for additional in vivo studies.