Wanasawas Pimphaka, Mitrevej Ampol, Sinchaipanid Nuttanan
Department of Manufacturing Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.
Pharmaceutics. 2022 May 15;14(5):1061. doi: 10.3390/pharmaceutics14051061.
In situ calcium pectinate-coated pellets were proposed by applying an alternate coating method to drug-layered pellets to achieve colon-specific drug delivery. Solution layering of metroprolol tartrate, a water-soluble model drug, on inert core pellets was achieved using a centrifugal granulator followed by successive alternate coating with pectin and calcium chloride layers using a fluidized bed bottom spray coater. The effect of the coating sequence on the drug release was studied in phosphate buffer pH 7.4 and 6.0. These test conditions were used to mimic the physiological environments in the distal small intestine and proximal colon, respectively. The results showed that the in situ calcium pectinate layer was successfully generated from the alternate coating of pectin and calcium layers after hydration to form gelation, which was able to control the drug release. The coating sequence played an important role in the drug release. The outermost pectin layer tended to retard the drug release whilst the outermost calcium layer accelerated the release regardless of the number of coating layers. These findings indicate that the release behavior followed the Higuchi model, with the drug release from the coated pellets described by a diffusion control mechanism. It is concluded that the success of the in situ calcium pectinate-coated pellets in controlling the drug release is due to the coating of the outermost layer with pectin and the maintenance of the optimum ratio of calcium to pectin upon hydration.
通过将交替包衣方法应用于药物层状微丸，提出了原位果胶酸钙包衣微丸以实现结肠特异性药物递送。使用离心造粒机在惰性核心微丸上进行酒石酸美托洛尔（一种水溶性模型药物）的溶液层积，然后使用流化床底部喷雾包衣机依次交替包被果胶层和氯化钙层。在pH 7.4和6.0的磷酸盐缓冲液中研究了包衣顺序对药物释放的影响。这些测试条件分别用于模拟远端小肠和近端结肠的生理环境。结果表明，果胶层和钙层交替包衣后，经水合形成凝胶，成功生成了原位果胶酸钙层，该层能够控制药物释放。包衣顺序在药物释放中起重要作用。无论包衣层数如何，最外层的果胶层倾向于延缓药物释放，而最外层的钙层则加速释放。这些发现表明，释放行为遵循Higuchi模型，药物从包衣微丸中的释放由扩散控制机制描述。得出的结论是，原位果胶酸钙包衣微丸在控制药物释放方面的成功归因于最外层用果胶包衣以及水合后维持钙与果胶的最佳比例。
