对pH和果胶酶敏感的结肠定位片的研制

Colon-specific tablets sensitive to pH and pectinase

目的:以盐酸小檗碱(BH)为模型药物,研制出具有良好结肠定位释药性能的结肠定位片。方法:以高酯化果胶(HMP)-羟丙甲基纤维素(HPMC)为骨架材料湿法制粒制备骨架片芯,以聚丙烯酸树脂Ⅱ-聚丙烯酸树脂Ⅲ-乙基纤维素为包衣材料制备骨架包衣片。通过体外释放试验,研究结肠定位片释药性能。结果:筛选出的BH结肠定位片在模拟胃液中2h无药物释放,在模拟小肠液中3h累积药物释放量<3%(n=3),而在模拟的结肠环境(加果胶酶或大鼠结肠内容物)19h药物完全释放。相应处方的双黄结肠定位片亦具有相似的释药性能。结论:以HMP-HPMC(3∶1,占片重60%)为骨架材料制备片芯后,包pH敏感衣层的结肠定位片显示出良好的结肠定位释药性能。

AIM： To develop an oral colon-specific drug delivery system（ OCDDS）, using berberine hydrochlo- ride（BH） as model drug, sensitive to pH and pectinase. METHODS： Matrix core tablets were prepared by wet granulation technique by use of HPMC solution as a binder and HMP-HPMC as the matrix materials, while colon- specific （coated matrix） tablets were prepared by coating the matrix core tablets with the mixture of Polyacrylic Resin I1, Polyacrylic Resin llI and Ethyl Cellulose in certain proportion. The characteristics of colon-specific tab- lets were evaluated by in vitro dissolution. RESULTS： The colon-specific tablets of BH did not release in gastric simulate buffer for 2 h ; the cumulative percent of drug released from colon-specific tablets in intestine simulate buff- er for 3 h was no more than 3% （n =3） ; in contrast, 19 h in the colon simulate buffer（with pectinex or rat caecal contents）, the rest drugs tablets contained were all released. Paralleling with BH colon-specific tablets, coptis root and baical skullcap root colon-specific tablets had the similar properties. CONCLUSION： The colon-specific tab- lets prepared in present study have nice characteristic of drugs releasing in colon.