5-氨基水杨酸果胶钙微丸的制备及粉体学性质与释药特征的考察

Preparation of 5-amino salicylic acid loaded calcium pectinate pellets and evaluation of their micromeritic properties and characteristics of the drug release behavior

目的考察含有5-氨基水杨酸的果胶钙骨架微丸的制备过程的影响因素以及微丸的粉体学性质与释药特征。方法采用挤出滚圆法制备5-ASA果胶钙微丸,通过考察含钙量不同的果胶钙微丸以及处方中果胶钙含量不同的微丸的粉体学性质和释药曲线,从而确定制备微丸的最佳处方。将果胶钙微丸与普通微丸(不含果胶钙)和含质量分数为3%的崩解剂的微丸在pH7.4 PBS中的释药曲线进行比较,并比较果胶钙微丸在pH7.4 PBS、含果胶酶及含大鼠盲肠内容物的pH7.4 PBS中的释药曲线,同时结合SEM法分析释药机理,从而评价果胶钙在微丸中的作用。结果当果胶钙的含钙量为15 mg.g-1,处方中果胶钙的含量质量分数为20%时,微丸成球性较好,且5-ASA果胶钙微丸在1 h内即可释放完全,其释药速度明显快于5-ASA普通微丸和含质量分数为3%崩解剂的5-ASA微丸,而在大鼠盲肠内容物存在的条件下,5-ASA果胶钙微丸0.5 h内便释放完全。结论果胶钙在微丸中能加快药物的释放,且具备一定的酶降解性能,可用于制备难溶性药物微丸及难溶性药物结肠定位制剂包衣微丸的丸芯。

Objective To investigate the influencing factors on preparation of 5-amino salicylic acid （ASA） loaded calcium pectinate （CAP） pellets by excursion-spheronizing method, and to evaluate the micromeritic properties and the drug release behavior for the resultant pellets. Methods The 5-ASA-（CaP） pellets were prepared with extrusion - spheronizing equipment. The optimal content of Ca in CaP and the maximum amount of CaP in pellets were selected by comparing the micromeritic properties and drug release profiles in vitro of pellets, which contained various amount of CaP and different content of Ca in CaP. Dissolution test of the CaP pellets, pellets without CaP, and pellets containing 3 % disintegrating agent were carried out in PBS of pH7.4. The drug release behavior from the CaP pellets was conducted in PBS of pH7.4, in PBS of pH7.4 with 6 g· L^- 1 domestic pectinase and in PBS of pH7.4 with 6 g·L^- 1 appendix material, respectively. Enzyme-decomposed capability of CaP pellets was compared. In addition, SEM was applied to analyze the mechanism of the drug release from CaP pellets and evaluate the function of CaP in pellets. Results When 20% of CaP was formulated in the pellets and Ca content in CaP was 15 mg·g^-1, the pellets showed a good degree of sphericity. The drug release from the 5-ASA-CaP pellets could be completed within 1 h, which was obviously faster than the pellets without CaP and the pellets containing 3 % disintegrating agent. Furthermore, when 6 g·L^- 1 of appendix material was added into the dissolution medium, the drug release from the 5-ASA-CaP pellets could be completed within 0.5 h. Conclusions CaP pellets can increase drug release rate and enzyme-decomposed, and can be a good candidate for the insoluble drug loaded system or the insoluble drug loaded cores of colonic targeting pellets