琥珀酸去甲文拉法辛缓释微丸胶囊的制备及微丸体外释药研究

摘要

目的：制备琥珀酸去甲文拉法辛（DVS）缓释微丸胶囊，并对微丸体外释药特性进行研究。方法：采用醇溶上药法制备DVS微丸，并进行微丸质量评价及粉体学性质研究。用乙基纤维素和羟丙甲基纤维素作为包衣材料，流化床包衣制备DVS缓释微丸，干燥后装入肠溶空心胶囊中，制得缓释微丸胶囊。考察缓释微丸的体外释药特性、不同干燥时间（1～24 h）和人工胃液对其释药的影响。结果：DVS微丸和DVS缓释微丸的膜表面均光洁、有散在分布的小孔。DVS微丸中DVS的含量为19.56％（RSD＝0.53％，n＝10），上药率为94％，堆密度为0.7921 g/ml，圆整度为7.84°，休止角为21.3°。DVS缓释微丸经不同时间干燥后的释药差异无统计学意义（P＞0.05），经人工胃液处理3 h后累积释放度降低；DVS缓释微丸释药规律符合一级动力学过程。结论：本方法成功制成具有缓释作用的DVS缓释胶囊，且制备过程中可不进行干燥。%OBJECTIVE:To prepare Desvenlafaxine succinate(DVS)sustained-release pellets capsules,and to investigate the release property in vitro of pellets. METHODS:The pellets containing DVS were prepared by alcohol solution. The quality and mi-cromeritics of DVS pellets were studied. Using ethylcellulose(EC)and hydroxypropyl methyl cellulose(HPMC)as coating materi-als,DVS sustained-release pellets were prepared by fluid-bed,and then put into enteric hollow capsule. The release property in vi-tro of DVS sustained-release pellets,and the effects of different drying time (1-24 h) and artificial gastric juice on drug release were investigated. RESULTS:DVS pellets and DVS sustained-release pellets were smooth and had scattered ostiole in surface. The content of DVS in DVS pellets was 19.56%(RSD=0.53%,n=10),and drug-loading rate was 94%;bulk density was 0.792 1 g/ml;roundness degree was 7.84 °;angle of repose was 21.3 °. There was no statistical significance in the difference of drug release for DVS sustained-release pellets after dried for different time (P>0.05),and accumulative release rate decreased 3 h after treated with artificial gastric juice;the release regularity of DVS sustained-release pellets fitted to first-order kinetic equation. CONCLU-SIONS:DVS sustained-release capsules are prepared successfully by this method,and can be not dried during preparation.