Department of Pharmaceutics, Shenyang Pharmaceutical University, Wen Hua Road No. 103, Shenyang 110016, Liaoning, People's Republic of China.
Int J Pharm. 2010 Nov 15;400(1-2):42-8. doi: 10.1016/j.ijpharm.2010.08.028. Epub 2010 Aug 27.
This study was performed to prepare high-dose nicotinic acid (NA) loaded sustained-release pellets coated with double polymer and simvastatin (SIM). The uncoated pellets were prepared by extrusion-spheronization and the double ethylcellucose (EC) films were coated in a bottom-spray fluidized bed coater. SIM was milled by wet grinding and then the milled suspension was layered on the coated pellets. Results showed that coated with 1.5% subcoating and 1% outer coating composed of EC and polyvinyl pyrrolidone K30 (PVP(K30)) in ratios of 5:1 and 2:1, NA release behavior was very similar to the reference (NER/S; SIMCOR, Abbott) in different media. And SIM was delivered more rapidly than that of the reference, while the SIM layer had no influence on NA release. During 6-month storage at 40°C/75% RH, the two drugs exhibited stable dissolution behavior. It was observed that the content uniformity of SIM was provided by the present preparation and SIM was stable if adding light magnesium oxide in the grinding procedure. Results indicated it was possible to prepare high-dose sustained-release NA pellets combined with little-dose immediate release SIM by spraying double EC polymer and SIM milled suspension on NA pellets in a bottom-spray fluidized bed coater, respectively.
本研究旨在制备载高剂量烟酸（NA）的双层聚合物包衣缓释微丸，并载有辛伐他汀（SIM）。未包衣微丸通过挤出滚圆法制备，双层乙基纤维素（EC）薄膜在底部喷雾流化床包衣机中包衣。SIM 通过湿磨粉碎，然后将粉碎的混悬液分层涂覆在包衣微丸上。结果表明，用 1.5%的次涂层和 1%的由 EC 和聚乙烯吡咯烷酮 K30（PVP（K30））组成的外层（比例为 5:1 和 2:1）进行包衣，NA 的释放行为与参比制剂（NER/S；SIMCOR，Abbott）在不同介质中非常相似。同时，SIM 的释放速度比参比制剂更快，而 SIM 层对 NA 的释放没有影响。在 40°C/75%RH 下储存 6 个月期间，两种药物均表现出稳定的溶出行为。观察到本制剂可以提供 SIM 的含量均匀度，如果在研磨过程中加入轻质氧化镁，SIM 是稳定的。结果表明，通过在底部喷雾流化床包衣机中分别将双层 EC 聚合物和 SIM 粉碎的混悬液喷涂在 NA 微丸上，可以制备载高剂量 NA 缓释微丸并载少量 SIM 速释的制剂。
