Faculty of Pharmacy & Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G 2E1, Canada.
Universidade São Francisco, Programa de Pós-graduação Stricto Sensu em Ciências da Saúde, Bragança Paulista, São Paulo, 12916-900, Brazil.
Int J Pharm. 2021 Aug 10;605:120857. doi: 10.1016/j.ijpharm.2021.120857. Epub 2021 Jul 3.
There are many hurdles in the development of generic formulations. In vitro biopredictive dissolution conditions together with alternative in vitro - in vivo relationship (IVIVR) approaches can be a powerful tool to support the development of such formulations. In this study, we hypothesized that the release profile of enteric coated (EC) formulations of pantoprazole in physiologically relevant bicarbonate buffer (BCB) would detect possible performance differences between test and reference formulations resulting in more accurate IVIVR results and predictability when compared to a pharmacopeial dissolution test. We correlated the in vitro performance of test and reference formulations (both in BCB and pharmacopeial phosphate buffer) with the in vivo data from a failed bioequivalence study. Test and reference formulations of EC pantoprazole tablets passed the USP dissolution criteria. However, they failed statistical similarity in vitro both in compendial and BCB. Bicarbonate buffer was additionally more discriminative while being more physiologically relevant. Having BCB as an additional test to evaluate EC products in vitro might improve the comparison of formulations. This can de-risk the development of generic EC formulations.
在仿制药制剂的开发过程中有许多障碍。体外生物预测溶解条件以及替代的体外-体内相关性（IVIVR）方法可以成为支持此类制剂开发的有力工具。在这项研究中，我们假设在生理相关的碳酸氢盐缓冲液（BCB）中，泮托拉唑肠溶片的释放曲线可以检测出测试和参比制剂之间可能存在的性能差异，从而在与药典溶出度测试相比时，产生更准确的 IVIVR 结果和可预测性。我们将测试和参比制剂（均在 BCB 和药典磷酸盐缓冲液中）的体外性能与一项失败的生物等效性研究中的体内数据相关联。EC 泮托拉唑片剂的测试和参比制剂均通过了 USP 溶出度标准。然而，它们在药典和 BCB 中均未能在体外达到统计学相似性。碳酸氢盐缓冲液具有更好的区分度，同时更具生理相关性。在体外评估 EC 产品时将 BCB 作为附加测试可能会改善制剂之间的比较。这可以降低开发仿制药 EC 制剂的风险。
