Pharmaceutical Technology R&D Division, Spera Pharma, Inc., 17-85, Jusohonmachi 2-chome, Yodogawa ku, Osaka, 532-0024, Japan.
AAPS PharmSciTech. 2022 Jun 8;23(5):157. doi: 10.1208/s12249-022-02311-y.
Gastroretentive drug delivery systems (GRDDS) get retained in the stomach for a long time, thus facilitating the absorption of drugs in the upper gastrointestinal tract. However, drugs that are difficult to dissolve or unstable in an acidic environment are not suitable for GRDDS. The current study designs GRDDS combined with a self-micro-emulsifying drug delivery system (SMEDDS) for drugs with solubility or stability problems in the stomach. The model drug fenofibrate was formulated into the optimized liquid SMEDDS composed of 50 w/w% Capryol PGMC, 40 w/w% Kolliphor RH40, and 10 w/w% Transcutol HP and solidified through adsorption on several porous adsorbents. In a dissolution medium at pH 1.2, the powdered SMEDDS using Fujicalin dissolved quickly and achieved higher drug dissolution than other adsorbents. Based on these results, a gastroretentive bilayer tablet consisting of a drug release layer and a swelling layer was designed. The drug release layer was formulated with the powdered SMEDDS and hydroxypropyl methylcellulose (HPMC) as a release modifier. HPMC was also added to the swelling layer as a water-swellable polymer. The dissolution rate depended on the viscosity of the HPMC in the drug release layer. The time for 90% drug release was extended from 3.7 to 12.0 h by increasing the viscosity grade of HPMC from 0.1 to 100 K. Moreover, the tablet swelled and maintained a size comparable to a human pylorus diameter or more for at least 24 h. This GRDDS could apply to a broader range of drug candidates.
胃滞留型药物传递系统（GRDDS）在胃中滞留时间较长，从而促进了上胃肠道药物的吸收。然而，在酸性环境中溶解度低或不稳定的药物不适合 GRDDS。本研究设计了将 GRDDS 与自微乳药物传递系统（SMEDDS）结合使用，用于解决在胃中溶解度或稳定性有问题的药物。模型药物非诺贝特被制成由 50 w/w% Capryol PGMC、40 w/w% Kolliphor RH40 和 10 w/w% Transcutol HP 组成的优化液态 SMEDDS，并通过吸附在几种多孔吸附剂上进行固化。在 pH 1.2 的溶解介质中，用 Fujicalin 粉末化的 SMEDDS 快速溶解，比其他吸附剂实现了更高的药物溶出度。基于这些结果，设计了一种由释药层和膨胀层组成的胃滞留双层片剂。释药层由粉末化的 SMEDDS 和羟丙基甲基纤维素（HPMC）作为释放调节剂制成。HPMC 也作为水膨胀聚合物添加到膨胀层中。溶出速率取决于释药层中 HPMC 的粘度。通过将 HPMC 的粘度等级从 0.1 增加到 100K，90%药物释放的时间从 3.7 小时延长到 12.0 小时。此外，片剂在至少 24 小时内膨胀并保持与人幽门直径相当或更大的尺寸。这种 GRDDS 可以应用于更广泛的候选药物。
