炎琥宁肠溶微丸的制备工艺研究

Study on preparation technique of enteric coating Potassium Sodium Dehydroandroan Drographolide Succinate pellets

目的用水分散体系包衣技术制备炎琥宁肠溶微丸给药系统。方法以微晶纤维素(MCC)为填充剂,SiO2为抗黏剂,40%乙醇为黏合剂,采用挤出滚圆法制备丸芯,正交试验设计优化处方和工艺;以Eudragit L 30 D水分散体为包衣材料,乙基纤维素(EC)为阻滞剂,PEG6000为增塑剂,采用流化床包衣法,包肠溶衣层。结果丸芯的最佳处方工艺为:炎琥宁∶MCC∶SiO2=7∶7∶5;挤出速度1 080 r/min,滚圆速度960 r/min,滚圆时间5 min;当EC与Eu-dragit L质量比为35∶65,增塑剂用量为1.71%,聚合物包衣增重为5%时,所制得炎琥宁肠溶微丸在人工胃液(pH1.0)中释放度<10%,在人工肠液(pH 6.8)中正常释放,2 h内释放大于80%,符合中国药典对肠溶制剂释放度的相关规定。结论调整丸芯及包衣的处方工艺参数可以制得体外释放行为符合药典规定的肠溶炎琥宁微丸。

Purpose To build up the Potassium Sodium Dehydroandroan Drographolide Succinate enteric coating sustained-release pellets delivery system by aqueous dispersion coating technique. Methods 1. Adopting MCC as vehicle, SiO2 as antisticking agent, appropriate amount of 40% ethanol, preparing the core of pellets by extrude-spheronization method and the formulation and manufacturing process were optimized by orthogonal design. 2. Preparing the coating material with Eudragit L 30 D, which is used as pore-forming agent, EC as blocker and PEG6000 as plasticizer. The pellets were coated by fluid-bed coating method. Results 1. The optimal formulation and manufacturing process of pelltes＇ core were as follows ： drug ： MCC ： SiO2 = 7 ： 7 ： 5, extruding rate ： 1 080 r/min, rounding rate ： 960 r/min, rounding time ： 5 min. 2. After the addition of EC ： Eu- dragit L = 35：65, the plasticizer is 1.71 % and weight gain is 5 %. The release in the gastric model fluid（pH 1.0） 〈 10%, and complete release （ 〉 80%） in the enteric model fluid（pH 6.8） was in two hours. The release behavior accords with the regulations on the release rate of enteric preparation in ChP. Conclusion By adjusting the formulation and the parameters of the process of pellet and coating, we can make enteric coating Potassium Sodium Dehydroandroan Drographolide Succinate sustained-release pellets. All this accords with the regulation of pharmacopedia in vitro release.