5-氨基水杨酸结肠定位双层包衣微丸的制备

Preparation of 5-Aminosalicylic Acid Donble Coated Colon-specific Pellets

目的制备5-氨基水杨酸(5-ASA)果胶壳聚糖聚电解质复合物(PEC)-尤特奇结肠定位双层包衣微丸。方法扩散实验考察PEC膜对传递系统释药速率的影响;考察PEC包衣微丸在大鼠盲肠内的生物降解性;考察膜溶胀性与阻滞释药能力和生物降解性的关系;制备双层包衣微丸并验证其结肠定位性能。结果扩散实验表明,在模拟小肠液中阻滞释药能力较强的3种处方为:A、果胶-壳聚糖Ⅰ=3:1,B、果胶-壳聚糖Ⅰ-HPMC=2:1:1,C、果胶-壳聚糖Ⅱ=2:1;膜降解实验表明PEC包衣微丸能被结肠微生物菌群所降解;溶胀实验显示,膜溶胀比与包衣微丸的释药速率和降解性之间不存在线性关系;模拟胃肠道传输的体外释药实验显示,PEC-尤特奇双层包衣微丸有效地在小肠中阻滞药物释放,在结肠中释药较快,具备双模式的释药特征。结论 5-ASA果胶壳聚糖PEC-尤特奇结肠定位双层包衣具有双模式的释药特征,具有良好的结肠定位性能。

OBJECTIVE To prepare 5-aminalsalisylic acid（5-ASA） colon-specific delivery system double coated with pectin-chitosan polyelectrolytecomplex（PEC）-Eudragit films.METHODS The influences of formulations of films on drug release of the delivery system in pH 6.8 PBS were inspected.The abilities of degradation of PEC coated pellets were determined.Relations among swelling capacities,drug release retarding abilities and the degradation abilities of the films were investigated.RESULTS Three colon-specifc charactersitic formulations of the most effective retarding drug release were：A.pectin-chitosanⅠ（with molecular weight of 5 lac,degree of deacetylation 72.3%）=3：1;B.pectin-chitosanⅠ-HPMC=2：1：1;C.pectin-chitosanⅡ（with molecular weight of 1 lac,degree of deacetylation 95.4%）=2：1.The degradation test of films indicated that pellets coated the three formulations with effective retarding drug releasing ability were degradated by colon micro flora.Swelling tests indicated that there were not obvious linearity relation among swelling scales,drug releasing and degradation capacities of the films.The in vitro dissolution simulating transit of the gastrointestinal indicated that double coated pellets effectively retarded drug release.CONCLUSION The 5-ASA pellets double coated by the PEC-Eudrgit have the bimodal drug release,and show favorable colon specific delivery ability.