马钱子碱双层渗透泵控释片的研制及处方优化

Preparation and Optimization of Brucine Push-pull Osmotic Pump Controlled Release Tablets Formulation

关键词:  马钱子碱  双层渗透泵  处方优化  正交试验  零级释放

Key words:  brucine  push-pull osmotic pump  prescription optimization  orthogonal test  zero-release profile

摘要:

目的 制备马钱子碱双层渗透泵控释片，通过正交试验优化处方，并探讨最佳处方的释药机制。方法 以累积释放度及释药曲线是否呈线性作为评价指标，单因素试验考察PEO N750、PEO Coagulant和致孔剂PEG 4000用量以及包衣增重对马钱子碱双层渗透泵控释片体外释药情况的影响。设计正交试验优化马钱子碱双层渗透泵控释片处方，并对最佳处方体外释药行为进行模型拟合。结果 正交试验结果表明，PEO N750用量对马钱子碱双层渗透泵控释片体外释药行为有显著性影响（P<0.05），最佳处方：PEO N750 175 mg，PEO Coagulant 65 mg，PEG 4000用量为11%，包衣增重7%。马钱子碱双层渗透泵控释片最佳处方在12 h内释药速率恒定，12 h内累积释放度达93.14%。结论 研制的马钱子碱双层渗透泵控释片在12 h内具有明显的零级释放特征，可有效控制马钱子碱缓慢、恒速释放。

Abstract:

OBJECTIVE To prepare brucine push-pull osmotic pump controlled release tablets, obtain optimal formulation by orthogonal design, and to investigate the release mechanism. METHODS The percent of cumulative release and whether the drug release curve was linear were used as the evaluation standard for the drug release profile in vitro. The effects of amounts of PEO N750, PEO Coagulant, PEG 4000 and coating weight were studied through single-factor method. Based on the single-factor study, the optimal formulation of brucine push-pull osmotic pump controlled release tablet was selected via orthogonal design. The release in vitro of the optimized formulation was also fitted to different models. RESULTS The results of orthogonal design showed that amounts of PEO Coagulant had significant effects on the drug release in vitro (P<0.05). The optimal prescription:PEO N750 was 175 mg, PEO Coagulant was 65 mg, PEG 4000 was 11%, weight gain of coating was 7%. The release rate of brucine push-pull osmotic pump controlled release tablets with optimized formulation was constant, and the cumulative release could reach 93.14%. CONCLUSION The prepared of brucine push-pull osmotic pump controlled release tablets show excellent zero-release profile in 12 h, which could control the release of brucine from push-pull osmotic pump tablets.