摘要
目的采用Box-Behnken设计-效应面法优化元胡止痛双层渗透泵片的处方。方法选择含药层聚氧乙烯N750含量、含药层氯化钠含量和包衣增重为因素,以12 h累积释放度和药物释放曲线拟合度为考察指标,建立多元线性模型考察各因素对制剂释药行为的影响;绘制二次多项式模型效应面图,确定优化处方并进行验证。结果二次多项式为最佳拟合模型,得到最优处方为:含药层聚氧乙烯N750含量为88 mg·片-1,氯化钠含量为27 mg·片-1,包衣增重为7.7%。3批优化处方中延胡索乙素12h平均累积释放度分别为78.68%、79.01%、78.93%,释药曲线线性拟合度r2分别为0.985 2、0.982 8、0.991 8;欧前胡素12 h平均累积释放度分别为79.12%、78.96%、79.35%,释药曲线线性拟合度R2为0.984 7、0.990 2、0.985 8。影响因素实验、加速实验和长期实验表明,该制剂稳定性良好。结论 Box-Behnken设计-效应面法可用于元胡止痛双层渗透泵片的处方优化。
OBJECTIVE To optimize the formulation of Yuanhu Zhitong push-pull osmotic pump tablets by Box-Behnken design- response surface method. METHODS The amounts of polyoxyethylene-N750 and sodium chloride in drug layer and coating weight were selected as factors and the 12 h accumulative drug release and fitting degree of release curves were selected as indexes, respective- ly. The effects of different factors on drug release were investigated by establishing multivariate linear model, and response surface of second order polynomial model was drawn to determine and validate the optimum formulation. RESULTS The second order polynomi- al model was the best fitting model. The optimum prescription was as follows ： 88 mg of polyoxyethylene-N750 in drug layer and 27 mg of sodium chloride in drug layer per tablet and 7.7% of coating weight. The 12 h cumulative release and fitting degree r2of drug relea- ses of imperatiorin of three batches of optimized products were 78.68%, 79. 01%, 78.93% and 0. 985 2, 0. 982 8, 0. 991 8, respec- tively. The 12 h cumulative release and fitting degree r2of drug releases of tetrahydropalmantin of three batches of optimized products were 79. 12% , 78.96% , 79. 35% and 0. 984 7, 0. 990 2, 0. 985 8, respectively. The preparation was proved good in stability by in- fluential factor test, accelerated test and long-term test. CONCLUSION The Box-Behnken design-response surface method can be used to optimize the formulation of Yuanhu Zhitong push-pull osmotic pump tablets.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2014年第16期1420-1425,共6页
Chinese Pharmaceutical Journal
基金
国家"十二五"重大新药创制科技重大专项经费资助课题(2013ZX09J13109-05C)
