盐酸甲氧氯普胺缓释微丸的制备研究

Study on the preparation of metoclopramide hydrochloride sustained-release pellets

目的 以Eudragit NE 30D为材料、Eudragit L 30D-55为致孔剂,制备盐酸甲氧氯普胺微丸。方法 通过外翻肠囊实验法,采用高效液相色谱法分析盐酸甲氧氯普胺在肠内的吸收情况,确定药物的剂型。采用流化床包衣技术,以溶出度为主要指标,通过中心复合设计-效应面法优化处方。结果 盐酸甲氧氯普胺大鼠肠道吸收方式是被动扩散,各肠段表观渗透系数大小依次为:结肠<十二指肠<回肠<空肠,可制备成微丸。然后以包衣增重和Eudragit NE 30D与Eudragit L 30D-55的比例为考察指标,获得最优处方为:包衣增重7%,Eudragit NE 30D与Eudragit L 30D-55的比例为25∶1。结论 本实验建立的处方优化模型预测性良好,制得的盐酸甲氧氯普胺微丸具有良好的性质,可以为工业化生产提供良好的实验基础。

Objective To optimize and evaluate the preparation of metoclopramide hydrochloride pellets with Eudragit NE 30D as material and Eudragit L 30D-55 as porogen.Methods The absorption of metoclopramide hydrochloride in the intestine was analyzed by high performance liquid chromatography(HPLC)through everted intestinal sac experiment method to determine the dosage form of metoclopramide hydrochloride.The formulation was optimized by central composite design response surface methodology with the dissolution rate as the main index.Results Metoclopramide hydrochloride was absorbed by rats intestine through passive diffusion,and the apparent permeability coefficient of each intestinal segment was:colon<duodenum<ileum<jejunum,which was suitable to be prepared into pellets.Taking coating weight gain and the ratio of Eudragit NE 30 d to Eudragit L 30D-55 as the evaluation index,the optimal formula was obtained as follows:coating weight gain 7%,the ratio of Eudragit NE 30D to Eudragit L 30D-55 was 25-1.Conclusion The formulation optimization model established in this experiment has good predictability,and the prepared metoclopramide hydrochloride pellets have good properties,which can provide a good reference for industrial production.