Box-Behnken效应面法筛选聚氧乙烯骨架缓释片处方和释药机制的研究  

Box-behnken Design for the Optimization of Formulation of Polyethylene Oxide Matrix Tablets and Its Release Mechanisms

作　　者：王福坚[1] 张自强 周建平[1] 姚静[1] 

机构地区：[1]中国药科大学药剂教研室,南京210009 [2]南京泽恒医药技术开发有限公司,南京210046

出　　处：《药学与临床研究》2013年第4期339-343,共5页Pharmaceutical and Clinical Research

摘　　要：目的:优化聚氧乙烯骨架片的处方并对释药机制进行研究。方法:以水溶性药物酒石酸美托洛尔为模型药物,釆用药物与聚氧乙烯等辅料混合均匀后直接压片的方法制备聚氧乙烯骨架片。以药物释放数据的零级方程拟合度R02和处方在1小时和24小时的累积释药百分率Q1h、Q24h为评价指标。用Box-Behnken效应面法筛选最优处方。获得最优处方的释放数据进行Higuchi equation、Korsmeyer equation、Peppas-Sahlin equation方程拟合。结果:优化处方是:酒石酸美托洛尔100 mg、聚氧乙烯170 mg、卡波姆65 mg、碳酸钠102 mg,按照该处方制备的酒石酸美托洛尔聚氧乙烯骨架片,对应的评价指标测得值与预测值的偏差小于5%。经验方程拟合和各种方法验证了骨架片的药物释放是扩散和溶蚀的协同作用。结论:利用Box-Behnken效应面法筛选酒石酸美托洛尔聚氧乙烯骨架片的处方的主方法是有效可行的,模型的预测值与理论值相符。药物的释放机制是扩散和溶蚀的协同作用。Objective： The purpose of this study was to optimize the prescription of the highly water soluble drugs metoprolol tartrate （MT） sustained-release tablets and investigate the mechanism of drug re lease. Methods： The water-soluble drug metoprolol tartrate as a model drug and the polyethylene oxides （PEO） were mixed in the matrix, and the test tablets were prepared using the uniform method of direct compression. Box-Behnken design was used for this study. Responses were measured in this study includ- ing the linear fitting degree （R） of cumulative release percentage versus time and the cumulative release percentages of 1 hour （QI） and 24-hour （Q24）. The mathematic kinetic models of MT release were elucidat- ed by fitting the release data to Higuehi equation, Korsmeyer equation or Peppas-Sahlin equation. Results： Optimal prescription included MT 100 rag, poly （ethylene oxide） 170 mg, carbomer polymer 65 mg, and sodi- um carbonate 102 rag. The predicted value of the deviation was less than 5%. The empirical equation fit- ting and a variety of methods verified the synergistic effect of the drug release in the matrix tablets as diffusion and dissolution. Conclusion： Box-Behnken response surface was an effective and feasible method for screening the highly water-soluble drugs MT sustained-release tablets formulation and the predictive values of the model were consistent with the experimental values. The drug release followed the zero-order kinetics and proved to be the synergistic result of diffusion and dissolution.

关 键 词：聚氧乙烯 水凝胶骨架片 BOX-BEHNKEN效应面法 释放机制 酒石酸美托洛尔 

分 类 号：R944.9[医药卫生—药剂学]