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目的以壳聚糖为酶触型结肠靶向给药系统的材料,研制可用于结肠靶向的多单元口服给药系统(迷你片),以期为结肠部位疾病治疗的药物输送提供重要参考。方法以结肠癌的治疗药物-吲哚美辛为模型药物,首先制备固体分散体,再采用直接压片法和包衣技术制备尤特奇-壳聚糖双层包衣结肠靶向迷你片,考察靶向迷你片在不同释放介质中的释药行为,采用小动物活体荧光成像技术考察制剂在体内的转运和吸收情况,并以比格犬为动物模型进行药动学研究和生物利用度评价。结果制备的壳聚糖多单元结肠靶向迷你片可以完整形态通过大鼠胃和小肠,并靶向在结肠部位缓慢释放,比格犬体内药动学数据表明,自制结肠靶向迷你片的释药时间显著延长,血药浓度平稳。结论本实验制备尤特奇-壳聚糖双层包衣多单元迷你片给药系统具有较好的结肠靶向性和缓释效果,可为治疗结肠疾病的制剂开发提供重要参考。

Preparation of Eudragit-Chitosan Bilayer Colon-Specific Multi-Dosage Mini Tablets

??OBJECTIVE To develop colon-targeting multi-dosage oral delivery system (mini tablet) using chitosan as the material for treatment of colon cancer. METHODS Indomethacin (IN) was chosen as a model drug. Firstly, IN solid dispersion was prepared, then Eudragit-chitosan bilayer coated colon targeting mini tablets were prepared by direct compression method and coating technology. The release profiles of the targeting mini tablets in different release media were studied. Small animal in vivo fluorescence imaging investigation was used to sudy the transport and absorption in rats. Beagle dogs were used as animal model to study the pharmacokinetics and bioavailability of the mini tablets. RESULTS The Eugragit-chitosan bilayer coated mini tablets maintained complete form when passing through the stomach and small intestine of rats, and targeted to the colon. The pharmacokinetic data in Beagle dogs showed that the mini tablets had delayed release and preserved steady absorption. CONCLUSION The prepared Eudragit-chitosan bilayer coated multi dosage oral colon mini tablets showed good colon targeting effect and sustained release, which can provide important reference for the treatment of colon diseases.