Liu Fang, Lizio Rosario, Schneider Uwe J, Petereit Hans-Ulrich, Blakey Peter, Basit Abdul W
Department of Pharmaceutics, The School of Pharmacy, University of London, 29/39 Brunswick Square, London WC1N 1AX, United Kingdom.
Int J Pharm. 2009 Mar 18;369(1-2):72-8. doi: 10.1016/j.ijpharm.2008.10.035. Epub 2008 Nov 17.
A novel double coating enteric system (comprising an inner layer of neutralised EUDRAGIT) L 30 D-55 and organic acid, and an outer layer of standard EUDRAGIT) L 30 D-55) was developed to provide fast dissolution in proximal small intestinal conditions. The mechanisms involved in the dissolution of the double coating were investigated and compared with a conventional single layer enteric coating and an hypromellose (HPMC) sub-coated enteric system. Rates of drug release from coated prednisolone pellets were established using USP II dissolution methods (0.1M HCl for 2h and subsequently pH 5.5 phosphate buffer) and the coating dissolution process was illustrated using confocal laser scanning microscopy (CLSM). The distribution of sodium, as a representative ion, in the double-coating system during dissolution was determined using scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDX). The double-coating system showed faster dissolution compared to the single coating and the HPMC sub-coated system in pH 5.5 buffer. The dissolution process of the double-coating was unusual; the inner coat dissolved before the outer coat and this accelerated the dissolution of the outer coat. During dissolution, sodium ions diffused from the inner coat to the outer coat. This migration of ions and the increased ionic strength and buffer capacity of the inner coat contribute to the rapid dissolution of the double-coating system.
一种新型双层包衣肠溶系统（由中和后的尤特奇L 30 D-55内层和有机酸以及标准尤特奇L 30 D-55外层组成）被开发出来，以在近端小肠环境中实现快速溶解。研究了双层包衣溶解所涉及的机制，并与传统单层肠溶包衣和羟丙甲纤维素（HPMC）亚包衣肠溶系统进行了比较。使用美国药典II溶出方法（0.1M盐酸2小时，随后是pH 5.5磷酸盐缓冲液）确定了包衣泼尼松龙微丸的药物释放速率，并使用共聚焦激光扫描显微镜（CLSM）展示了包衣溶解过程。使用扫描电子显微镜/能量色散X射线光谱（SEM/EDX）测定了溶解过程中作为代表性离子的钠在双层包衣系统中的分布。在pH 5.5缓冲液中，双层包衣系统比单层包衣和HPMC亚包衣系统显示出更快的溶解速度。双层包衣的溶解过程不同寻常；内层包衣在外层包衣之前溶解，这加速了外层包衣的溶解。在溶解过程中，钠离子从内层包衣扩散到外层包衣。这种离子迁移以及内层包衣离子强度和缓冲能力的增加有助于双层包衣系统的快速溶解。
