中心复合设计-效应面法优化非洛地平缓释片处方  

Formulation Optimization of Felodipine Extended-release Tablets by Central Composite Design-response Surface Methodology

作　　者：谢向阳[1,2] 张红[1] 杨小松[1] 刘祖雄[1] 陈鹰[1] 

机构地区：[1]广州军区武汉总医院药剂科,430070 [2]军事医学科学院毒物药物研究所,北京100850

出　　处：《医药导报》2012年第11期1477-1480,共4页Herald of Medicine

摘　　要：目的采用中心复合设计-效应面法优化非洛地平缓释片处方。方法以羟丙甲基纤维素(HPMC)K4M和HPMC 100LV的用量为考察因素,以1,4,8 h的累积释放度(Y1h、Y4h、Y8h)为考察指标,利用二因素三水平中心复合设计-效应面法优化处方,并采用f2相似因子对自制片剂和原研制剂的体外释放度进行比较。结果 HPMC K4M和HPMC100LV的用量各占片剂质量的20.0%和10.0%时,所得缓释片各时间点释放度符合标准;自制片剂和原研制剂在不同释放介质中的释放度相似因子f2分别为70.87,74.19,59.68,69.25。结论 HPMC K4M和HPMC 100LV以一定比例联合使用可以有效控制药物释放,采用中心复合设计-效应面法优化的处方预测性良好,制得的非洛地平缓释片体外释放符合要求。Objective The purpose of this study was to optimize the formulation of the felodipine extended-release tablets.Methods The felodipine extended-release tablets were prepared by employing the mixture of hydroxypropyl methylcellulose（HPMC） K4M and HPMC 100LV as the basic matrix materials.Factors that affected drug release were investigated.Thereafter,a central composite design-response surface methodology（CCD-RSM） was applied to optimize the formulation of the felodipine extended-release tablets.The release rate of the extended-release tablets and control tablets were compared by a similarity factor（f2 value）.Results The optimized formulation contained 20.0% of HPMC K4M and 10.0% of HPMC 100LV of the total weight and accumulative release percentages at 1,4,8 h were consistent with the criteria,which was 5%~30%,45%~70%,no less than 80%,respectively.The f2 for the extended-release tablets and control tablets in different solvents were 70.87,74.19,59.68,69.25.Conclusion Combing HPMC K4M and HPMC 100LV at a certain rate can effectively control drug release and the central composite design-response surface methodology is successfully used to optimize the formulation of felodipine extended-release tablets,which complying with requirements of the USP.

关 键 词：非洛地平 缓释片 羟丙甲基纤维素 中心复合设计-效应面法 

分 类 号：TQ450.1[化学工程—农药化工] R972[医药卫生—药品]