美吡双胍三层缓释片的研制和体内外评价  

Preparation and in vivo/in vitro evaluation of Gimepiride,Pioglitazone and Metformin sustained-release tablets

作　　者：宗太丽[1,2] 易中宏[2,3] 林羽[2,3] 张涛[2,3] 何勤[1] 

机构地区：[1]四川大学华西药学院,四川成都610041 [2]重庆医药工业研究院有限责任公司,重庆400061 [3]重庆市化学制药工程技术研究中心,重庆400061

出　　处：《华西药学杂志》2010年第4期409-412,共4页West China Journal of Pharmaceutical Sciences

摘　　要：目的研制由格列美脲、盐酸吡格列酮和盐酸二甲双胍组成的三层缓释片(美吡双胍缓释片),并研究其药剂学性质。方法以HPMC为骨架材料制备盐酸二甲双胍缓释层,采用三层压片技术,将其与格列美脲和盐酸吡格列酮制成的速释层和由微晶纤维素组成的隔离层制成三层片。用HPLC测定格列美脲和盐酸吡格列酮的溶出度、UV测定盐酸二甲双胍的体外释放、LC-MS测定Beagle犬随机交叉口服单剂国外样品(Triexer)和自制样品后血浆中盐酸二甲双胍的浓度,推算药动学参数。结果国外样品和自制样品的有关药动学参数如下:t1/2分别为14.74±4.95、11.37±3.89h;Cmax为15.158±3.584、12.967±1.752μg·mL-1;Tmax为2.83±0.61、3.25±0.99h;AUC0-t为90.140±20.736、90.155±14.817μg·mL-1·h。结论研制的美吡双胍缓释片具有速释和缓释作用,与国外样品生物等效,达到了设计要求。OBJECTIVE To prepare a sustained-release trilayer tablet comprising Gimepiride,Pioglitazone and Metformin and study its pharmaceutical characteristics.METHODS HPMC was used to prepare Metformin hydrochloride sustained-release layer.Gimepiride and Pioglitazone hydrochloride were prepared in rapid-release layer.Microcrystalline cellulose was used in isolated layer.The trilayed tablets were prepared by triple compression technology.The dissolution of Gimepiride and Pioglitazone hydrochloride were detected by HPLC.The in vitro-release of Metformin hydrochloride was detected by UV.In a randomized,crossover design,a single oral dose of Triexer^TM or Gimepiride,Pioglitazone and Metformin sustained-release trilayer tablets was given to 6 Beagle dogs and plasma concentration of Metformin hydrochloride was detected by LC-MS.Pharmacokinetic parameters were estimated by DAS 2.0.1 pharmacokinetic program.RESULTS The peak levels（Cmax） after administration of Triexer^TM and Gimepiride,Pioglitazone and Metformin sustained-release trilayer tablets averaged 15.158 ± 3.584 μg·mL^-1 and 12.967 ± 1.752 μg·mL^-1 at 2.83 ± 0.61 h and 3.25 ± 0.99 h,respectively.The mean elimination half lives（t1/2 Ke） were found to be 14.74 ± 4.95 h and 11.37 ± 3.89 h,respectively.AUC0-t were calculated to be 90.140 ± 20.736 μg·mL^-1·h and 90.155 ± 14.817 μg·mL^-1·h,respectively.CONCLUSION The formulated Gimepiride,Pioglitazone and Metformin sustained-release trilayer tablets exhibited both sustained-and rapid-release characteristics in vitro.As designed,the formulated Gimepiride,Pioglitazone and Metformin sustained-release trilayer tablets and TriexerTM were bioequivalence.

关 键 词：格列美脲 盐酸吡格列酮 盐酸二甲双胍 三层缓释片 生物等效 

分 类 号：R94[医药卫生—药剂学]