The biorelevant simulation of gastric emptying and its impact on model drug dissolution and absorption kinetics.,European Journal of Pharmaceutics and Biopharmaceutics

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The biorelevant simulation of gastric emptying and its impact on model drug dissolution and absorption kinetics.
European Journal of Pharmaceutics and Biopharmaceutics ( IF 4.4 ) Pub Date : 2020-02-10 , DOI: 10.1016/j.ejpb.2020.02.002
Helena Vrbanac ₁ , Jurij Trontelj ₁ , Sandra Berglez ₂ , Boštjan Petek ₂ , Jerneja Opara ₂ , Rebeka Jereb ₂ , Dejan Krajcar ₂ , Igor Legen ₂

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The highly variable physiological conditions within the gastrointestinal tract can cause variable drug release and absorption from the orally administrated dosage forms. The emptying of the gastric content is one of the most critical physiological processes, dictating the amount of the active ingredient available for absorption into the systemic circulation. In this study, we prepared two water gastric emptying regimes on advanced gastric simulator (AGS) with programmable "pyloric" valve. Gastric emptying regimes were designed in such a way to capture the main findings of the MRI (magnetic resonance imaging) in vivo studies, conducted under fasted conditions according to the EMA and FDA guidelines for bioavailability and bioequivalence studies. Four immediate release formulations containing a model drug of BCS class III were tested. Comparative dissolution tests were also performed with the USP2 apparatus. In vitro release profiles were compared to the in vivo data in order to evaluate the importance of gastric emptying for subsequent absorption of the active substance from the tested formulations. Our bio-relevant in vitro dissolution model showed good discriminatory power for all of the tested formulations. Moreover, a better relation to in vivo data was achieved with AGS with respect to the tested conventional dissolution method.

中文翻译：

胃排空的生物相关模拟及其对模型药物溶解和吸收动力学的影响。

胃肠道内高度可变的生理状况可引起口服给药剂型的可变药物释放和吸收。胃内容物的排空是最关键的生理过程之一，决定了可吸收进入体循环的活性成分的量。在这项研究中，我们在带有可编程“幽门”瓣膜的高级胃模拟器（AGS）上准备了两种水胃排空方案。胃排空方案的设计旨在捕获MRI（磁共振成像）体内研究的主要发现，该研究是根据EMA和FDA生物利用度和生物等效性研究指南在禁食条件下进行的。测试了包含BCS III类模型药物的四种速释制剂。还使用USP2仪器进行了比较溶出度测试。将体外释放曲线与体内数据进行比较，以评估胃排空对于随后从测试制剂吸收活性物质的重要性。我们与生物相关的体外溶出度模型对所有测试制剂均显示出良好的区分能力。此外，相对于已测试的常规溶出方法，AGS与体内数据之间的关系更好。我们与生物相关的体外溶出度模型对所有测试制剂均显示出良好的区分能力。此外，相对于已测试的常规溶出方法，AGS与体内数据之间的关系更好。我们与生物相关的体外溶出度模型对所有测试制剂均显示出良好的区分能力。此外，相对于测试的常规溶出方法，使用AGS可以更好地与体内数据建立联系。

更新日期：2020-02-10

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