湖北科技学院学报（医学版）

目的 制备pH依赖-酶触发型黄芩苷结肠靶向微丸，并优化工艺处方。方法 以目标微丸收率及圆整度为综合评价指标，用正交实验优化丸芯制备工艺；以累积体外释放度为评价指标，采用Box-Behnken响应面法优化包衣工艺。结果 正交实验得到的优化工艺处方为：黄芩苷用量为18%,微晶纤维素与乳糖之比为5∶1,滚圆时间为5min; Box-Behnken响应面法确定的最优包衣工艺处方为：丙烯酸树脂Ⅲ∶抗性淀粉RS3(2∶1),增塑剂用量17.1%,包衣增重29.8%,老化时间1.6h。最优工艺处方制备的样品在人工小肠液(pH6.8磷酸盐缓冲液)累积体外释放率约为2.9%,在人工结肠液(pH7.6磷酸盐缓冲液)累积体外释放率约为93.0%;在(含有胰蛋白酶)模拟肠液体累计释放度为2.9%,在(4%盲肠内容物法制备)模拟结肠液32h时累积释放度达70.37%,证明此微丸具有pH依赖及酶触发性。结论 正交实验结合Box-Behnken响应面法可用于黄芩苷结肠靶向微丸的制备，且最优处方得到的微丸具有pH依赖及酶触发性。

Objective To prepare pH-dependent and enzyme-triggered baicalin colon-targeted micropellets and optimize the process prescription.Methods The target pellet yield and roundness were taken as comprehensive evaluation indicators, and the pellet preparation process was optimized by the orthogonal experiment.The cumulative in vitro release was taken as the evaluation indicator, and the Box-Behnken response surface methodology was used to optimize the coating process.Results The optimized process formula obtained by the orthogonal experiment was as follows: the dosage of baicalin was 18%,the ratio of microcrystalline cellulose to lactose was 5∶1,and the spheronization time was 5 minutes.The optimal coating process formula determined by Box-Behnken response surface methodology was: acrylic resin Ⅲ∶resistant starch RS3(2∶1),plasticizer dosage 17.1%,coating weight gain of 29.8%,and aging time of 1.6 hours.The samples prepared by the optimal process formula had a cumulative in vitro release rate of about 2.9% in artificial intestinal fluid(pH 6.8 phosphate buffer) and a cumulative in vitro release rate of about 93.0% in artificial colonic fluid(pH 7.6 phosphate buffer);the cumulative release in simulated intestinal fluid(containing trypsin) was 2.9%,and the cumulative release in simulated colonic fluid(prepared by 4% cecal content method) at 32h was 70.37%,proving that the microcapsules were pH-dependent and enzyme-triggered.Conclusion The orthogonal experiment combined with Box-Behnken response surface method can be used to prepare baicalin colon-targeted micropellets, and the optimal micropellets are pH-dependent and enzyme-triggered.