氢溴酸高乌甲素双层渗透泵控释片的制备与处方优化

Preparation and optimization of formulation for lappaconitine hydrobromide push-pull osmotic pump controlled release tablets

目的制备氢溴酸高乌甲素双层渗透泵控释片,并优选最佳处方。方法以累积释放度为评价指标,设计单因素实验考察聚氧乙烯N750(PEO N750)、聚氧乙烯WSR303(PEO WSR303)、增塑剂用量及包衣增重对释药行为的影响。在单因素考察的基础上设计正交试验优化处方,对优化后处方的体外释药行为进行模型拟合。结果正交试验结果显示,包衣增重对释药行为影响显著(P<0.05)。最佳处方为:含药层氢溴酸高乌甲素20 mg,PEO N750用量为160 mg,NaCl为30mg;助推层中PEO WSR303用量为75mg,NaCl为20mg;增塑剂PEG 4000用量为10%,包衣增重5%。氢溴酸高乌甲素双层渗透泵控释片在12h内释药速率恒定,药物基本释放完全(95.02%)。结论氢溴酸高乌甲素双层渗透泵控释片工艺稳定,体外释药行为在12h内具有零级释放特征(r=0.992 1),达到控释要求。

Objective To prepare lappaconitine hydrobromide push-pull osmotic pump controlled release tablets and screen for the optimal formulation. Methods The percent of cumulative release was used as the evaluation index for the drug release profile in vitro. The effects of PEO N750, PEO WSR303, and plasticizer amounts and coating weight gain on the releasing behavior were investigated through single-factor method. Based on single-factor study on the compositions, the optimal formulation for lappaconitine hydrobromide push-pull osmotic pump controlled release tablet was selected via orthogonal design. The in vitro release of the optimized formulation was also fitted to different models. Results The results of orthogonal design indicated that coating weight gain had a significant effect on the drug release in vitro （P〈0. 05）. The optimal formula was as follows： lappaconitine hydrobromide 20 mg, PEO N750 160 mg, NaCl 30 mg in drug layer; PEO WSR303 75 mg, NaCl 20 mg in the push layer; and plasticizer PEG 4000 was 10% and weight gain was 5% in the coating composition. The release rate of the tablets with optimized formulation was constant within 12 h, and the cumulative release could reach 95. 02%. Conclusion The current method to prepare lappaconitine hydrobromide push-pull osmotic pump controlled release tablets is stable, and the in vitro drug release has an excellent zero-release profile within 12 h （r=0. 992 1）, which meets the standard for controlled release.