Freie Universität Berlin, Kelchstrasse 31, 12169 Berlin, Germany.
Freie Universität Berlin, Kelchstrasse 31, 12169 Berlin, Germany; University of Sulaimani, College of Pharmacy, Sulaimani, Iraq.
Int J Pharm. 2019 Oct 5;569:118520. doi: 10.1016/j.ijpharm.2019.118520. Epub 2019 Jul 27.
The objective of this study was to investigate the applicability of water-insoluble polymers as binders for pellet drug layering to extend the drug release. Carbamazepine was layered on sugar cores in fluidized bed coater using isopropanol (IPA):water solution or aqueous dispersion of ethylcellulose, polyvinyl acetate or ammonium-methylmethacrylate copolymer. Carbamazepine release was extended with all investigated water-insoluble polymers used as binder, without an additional coating layer. Drug release from pellets layered using IPA:water polymer solutions was dependent on polymer properties such as lipophilicity and pore-forming components, while from those layered with aqueous polymer dispersions, the release was dependent on the completeness of film formation during drug layering. Curing effect was observed only for pellets layered with Aquacoat® ECD and Eudragit® RS 30D. The drug release was not affected by compression when pellets were prepared with the flexible polymers Kollidon® SR or Kollicoat® SR 30D, however, it increased when brittle polymers such as ethylcellulose or Eudragit® RS were used. This problem could be minimized by using a higher amount of the binder, addition of a plasticizer or using polymers of higher viscosity grade. In conclusion, the use of water-insoluble polymers as binder for pellet drug layering is an effective tool to extend the drug release without additional coating step.
本研究旨在探讨水不溶性聚合物作为包衣辅料在流化床包衣机上药层造粒以延长药物释放的适用性。采用异丙醇(IPA):水溶液或乙基纤维素、聚醋酸乙烯酯或甲基丙烯酸铵共聚物的水性分散体,在流化床包衣机上将水不溶性聚合物作为包衣辅料将卡马西平包埋于糖芯上。所有考察的水不溶性聚合物都可以作为包衣辅料延长药物的释放,而无需额外的包衣层。用 IPA:水聚合物溶液包埋的颗粒的药物释放取决于聚合物的性质,如亲脂性和成孔成分,而用水性聚合物分散体制备的颗粒的药物释放则取决于药物包埋过程中膜的形成完整性。仅用 Aquacoat® ECD 和 Eudragit® RS 30D 包埋的颗粒观察到固化效应。当用柔韧性聚合物 Kollidon® SR 或 Kollicoat® SR 30D 制备颗粒时,药物释放不受压缩的影响,但当使用脆性聚合物如乙基纤维素或 Eudragit® RS 时,药物释放会增加。通过使用更高量的赋形剂、添加增塑剂或使用更高粘度等级的聚合物可以最小化此问题。总之,水不溶性聚合物作为包衣辅料在流化床包衣机上药层造粒是一种延长药物释放的有效工具,无需额外的包衣步骤。