目的 制备米非司酮胃滞留缓释微丸片,并对其体外释药性质进行考察。方法 采用挤出滚圆法制备米非司酮载药丸芯,对载药丸芯进行缓释功能层和黏附功能层包衣,得到米非司酮胃滞留缓释微丸;采用湿法制粒制备米非司酮速释颗粒,将米非司酮胃滞留缓释微丸、米非司酮速释颗粒外加辅料混合后压制成片剂,并从多个方面对米非司酮胃滞留缓释微丸片的体外释放进行考察。结果 米非司酮溶解度随pH变化的拐点为pH 3.0;米非司酮原料微粉化导致其溶解速率提升和瞬时溶解度增加;米非司酮胃滞留缓释微丸片的速释部分释放速率比普通片更高,缓释部分比普通片持续时间更长,在猪胃黏膜上的滞留时间也大大延长;加速条件下的稳定性与上市包装的米非司酮普通片无差异。结论 制备的新型米非司酮胃滞留缓释微丸片体外释药研究显示该微丸片的生物利用度高于普通片,使个体差异降低。
Abstract
OBJECTIVE To prepare mifepristone gastric retentive multi-unit pellet system (MUPs), and study its release behaviors in vitro. METHODS A sustained release layer and mucous adhesive layer were coated onto extrusion spherized mifepristone pellets. The gastric retentive sustained release pellets were mixed with granules which were wet granulated from micronized mifepristone and compressed into MUPs tablets. Investigation and evaluation of the in vitro release of mifepristone MUPs tablets were carried out from different aspects.RESULTS The turning point of pH value for the solubility of mifepristone was 3.0.Micronized mifepristone showed higher dissolving rate and apparent solubility.The gastric retentive mifepristone MUPs tablets had faster release than marketed mifepristone tablets. The in vitro adhesive experiment with pig stomach showed that mucous adhesive mifepristone pellets could be entrapped into the gastric mucous and retained for a long time. The accelerated stability study showed that mifepristone MUPs tablets were as stable as marketed mifepristone tablets.CONCLUSION Novel mifepristone gastric retentive MUPs tablets are successfully prepared.The release characteristics in vitro indicate that the product may have higher bioavailability than marketed mifepristone tablets with significantly lower variability.
关键词
米非司酮 /
胃滞留缓释微丸片 /
流化床包衣 /
体外释药
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Key words
mifepristone /
gastric retention sustained-release pellet tablet /
fluidized bed bottom-spray /
in vitro release
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中图分类号：
R944
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参考文献
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脚注
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基金
广东省科技厅对外科技合作项目:中德合作-缓控释给药技术研发平台(NO 粤科规划字[2012]98号)
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