Cui Cheng, Sun Jiabei, Wang Xueqing, Yu Zhenxi, Shi Yaqin
National Institutes for Food and Drug Control, Beijing, China.
Drug Clinical Trial Center, Peking University Third Hospital, Beijing, China.
Dose Response. 2020 Mar 4;18(1):1559325820908980. doi: 10.1177/1559325820908980. eCollection 2020 Jan-Mar.
This study was performed to explore factors influencing the release of the proton pump inhibitor omeprazole from enteric-coated capsules in vitro and absorption in vivo in beagle dogs. Enteric-coated pellets with different enteric coating materials and coating levels were designed and prepared. All self-prepared formulations were characterized in vitro as well as in vivo and compared to the brand and generic commercial products. Evaluation of the corresponding release profiles suggested that coating material was the most critical factor. Enteric coating level determined the lag time before initiation of drug release, and subcoating level affected the drug release rate. Pharmacokinetic studies were performed in beagle dogs to further confirm the influence of formulation factors on drug absorption. Medium at pH 6.8 was a more biorelevant condition for in vitro drug release tests, although medium at pH 6.0 was better for discriminating release profiles of different formulations. A multiple level C in vitro/in vivo correlation was preliminarily established by which T and C of omeprazole formulations could be predicted with release parameters such as T and T. These results may facilitate quality evaluation and potentially improve the clinical efficacy of generic omeprazole products.
本研究旨在探讨影响质子泵抑制剂奥美拉唑肠溶胶囊体外释放及在比格犬体内吸收的因素。设计并制备了具有不同肠溶包衣材料和包衣水平的肠溶微丸。所有自制制剂均进行了体外和体内表征，并与品牌和仿制药商业产品进行了比较。对相应释放曲线的评估表明，包衣材料是最关键的因素。肠溶包衣水平决定了药物释放开始前的滞后时间，而底包衣水平影响药物释放速率。在比格犬身上进行了药代动力学研究，以进一步证实制剂因素对药物吸收的影响。pH 6.8的介质对体外药物释放试验来说是更具生物相关性的条件，尽管pH 6.0的介质更有利于区分不同制剂的释放曲线。初步建立了多级体外/体内相关性，据此可以用诸如T和T等释放参数预测奥美拉唑制剂的T和C。这些结果可能有助于质量评估，并有可能提高奥美拉唑仿制药产品的临床疗效。
