盐酸曲美他嗪缓释制剂的研制

Sustained-release Preparations of Trimetazidine Hydrochloride

本试验制备了载盐酸曲美他嗪(1)的2种缓释制剂,分别是采用湿法制粒制备的缓释片剂和基于缓释包衣微丸的胶囊剂,后者是将采用离心造粒法制备的1缓释包衣微丸灌装而得。以体外释放度为指标,利用星点设计-效应面法优化了微丸包衣材料中Eudragit NE 30D与羟丙甲纤维素的比例及包衣增重。以原研1缓释片(Vasorel MR)为参比,对比了2种自制缓释剂型在水、0.1 mol/L盐酸、p H 4.5乙酸盐缓冲液和p H 6.8磷酸盐缓冲液中释放曲线的相似性。结果显示,2种自制品与原研缓释片在4种介质中的释放行为相似。Beagle犬体内药动学研究结果显示,1缓释片和缓释胶囊相对于原研1缓释片的口服生物利用度为(96.8±15.9)%和(101.5±16.7)%。

Two sustained-release formulations of trimetazidine hydrochloride （1） were prepared in this paper, one was the sustained-release tablets prepared by wet granulation method, the other was capsules based on the sustained- release coating pellets. The coating pellets were prepared by centrifugal granulation method and filled into gelatin capsules. Central composite design-response surface methodology was adopted to screen the optimal ratio of Eudragit NE 30D to hypromellose in coating layer and weight gain with in vitro release as the index. The similarities of in vitro release behaviors of two self-made formulations and the listed reference drug （Vasorel MR） in water, 0.1 mol/L HC1, pH 4.5 acetate buffer and pH 6.8 phosphate buffer were evaluated and compared. The results showed that the in vitro release behaviors of two self-made formulations in four media were similar to that of Vasorel. In vivo pharmacokinetic results in Beagle dogs showed that compared with Vasorel, the oral bioavailabilities of the sustained-release tablets and capsules of 1 were （96.8±15.9） % and （101.5±16.7） %, respectively.