5-氨基水杨酸结肠定位给药酶控释小丸的制备与体外释放

目的：用水分散体包衣技术制备5-氨基水杨酸(5-ASA)结肠定位释放小丸给药系统。方法：乙基纤维素水分散体(Surlease)和直链淀粉(Amylosf)为控释包衣材料，邻苯二甲酸二乙酯为增塑剂，使用流化床包衣设备，制备酶控释的结肠定位释放小丸，研究小丸在模拟人体胃肠道环境中的释放度，并观察游离包衣膜的消化性。结果：此种小丸在模拟胃肠道上部的介质中不释药，在模拟结肠介质条件下3h释药80％以上，10h内释药完全，具有脉冲释药特征。药物的释放时滞由衣膜厚度和衣膜处方组成控制。增加衣膜厚度以及处方中SurleaseE的用量，可延长释药时滞。膜的消化性试验表明，释放机制是衣膜中Amylose被结肠菌酶特异性降解而使衣膜破裂释药。结论：包衣液中加入被结肠酶特异性降解的Amylose可以使小丸具有结肠定位释放的特性。

Preparation of 5-amino salicylic acid(5-ASA) colon-specific targeting enzyme-controlled release pellets and its in vitro release

Objective:To prepare 5 ASA colon specific targeting pellets by using aqueous dispersion coating process.Methods:5 ASA colon specific targeting enzyme controlled release pellets was prepared by a fluid bed coater,using ethylcellulose aqueous dispersion(Surlease) and Amylose as the controlled coating meterials,using diethyl o phthalate as the plasticizer.Its dissolution rate in vitro was studied in simulating gastrointestinal circumstances and adding the colon enzyme.The digestibility of free coating film was also studied in simulated colon circumstances.Results:Data obtained showed that the pellets were not released in upper gastrointestinal juice,however,over 80% of them were released in 3h in simulated colon circumstances and completely released within 10h.Drug release was due to the decomposition of amylose in the coating membrane by colon enzyme.The thicker the membrane and the more the amount of Surlease,the longer the lag time.The mechanism of release has been confirmed by digestibility of the free coating film.Conclusion:The colon specific targeting enzyme controlled release pellets could be prepared by adding amylose that can be decomposed by a colon specific enzyme,to the coating solution.