格列美脲片体内外一致性评价研究  

In vitro and in vivo consistency study of Glimepiride tablets

作　　者：施猛 孙长山[1] 马鹏程 曹义海 SHI Meng;SUN Changshan;MA Pengcheng;CAO Yihai(Shenyang Pharmaceutical University,Shenyang 110016,China;Yangtze River Pharmaceutical Group Guangzhou Hairui Pharmaceutical Co.,Ltd.,Guangzhou 510000,China;Hospital for Skin Diseases,Institute of Dermatology,Chinese Academy of Medical Science and Peking Union Medical College,Nanjing 210042,China)

机构地区：[1]沈阳药科大学,辽宁沈阳110016 [2]扬子江药业集团广州海瑞药业有限公司,广东广州510525 [3]中国医学科学院皮肤病医院,江苏南京210042

出　　处：《广东药科大学学报》2025年第2期24-29,共6页Journal of Guangdong Pharmaceutical University

摘　　要：目的考察格列美脲片自制制剂与参比制剂的体外溶出行为及体内生物等效性,验证其质量一致性。方法体外研究采用经验证的溶出度检测方法,在pH 1.2盐酸溶液+1%吐温80、pH 6.8磷酸盐缓冲液及pH 7.8磷酸盐缓冲液3种介质中测定溶出曲线,并通过相似因子(f_(2))分析一致性;体内研究采用随机、开放、双周期交叉设计,纳入健康受试者进行空腹与餐后生物等效性试验,测定C_(max)、AUC_(0-t)、AUC_(0-∞)等药动学参数,并评估几何均值比的90%置信区间。结果自制制剂与参比制剂在3种介质中溶出曲线相似(f_(2)均>50),体外溶出一致;C_(max)、AUC_(0-t)和AUC_(0-∞)的几何均值比90%置信区间分别为空腹状态下的98.89%~124.98%和83.53%~100.61%,餐后状态下为96.13%~103.86%,均符合80.00%~125.00%的生物等效性标准。试验期间安全性良好,无严重不良事件。结论格列美脲片自制制剂与参比制剂在体外溶出行为及体内药动学参数上均具有一致性,可为临床提供安全经济的替代选择。Objective To evaluate the in vitro dissolution behaviors and in vivo bioequivalence of generic formulation of Glimepiride compared with the reference formulation to verify their consistency in quality.Methods A validated method for dissolution testing was employed for in vitro studies.The dissolution curves were measured in three different media:pH 1.2 hydrochloric acid solution+1% Tween 80,pH 6.8 phosphate buffer,and pH 7.8 phosphate buffer.Consistency was analyzed using the similarity factor(f_(2)).An open-label,two-period,randomized crossover bioequivalence trial was employed for in vivo studies,involving healthy subjects in both fasting and fed states.Pharmacokinetic parameters such as C_(max),AUC_(0-t),and AUC_(0-∞)were measured,and the 90%confidence intervals of the geometric mean ratios were assessed.Results The dissolution curves of the generic and the reference preparations in three dissolution media were similar(f_(2)>50),indicating consistent in vitro dissolution behaviors.The 90% confidence intervals of the geometric mean ratios for C_(max),AUC_(0-t),and AU_(C0-∞)were 98.89%-124.98% and 83.53%-100.61% under fasting conditions,and 96.13%-103.86% under fed conditions,respectively,all of which met the bioequivalence criteria of 80.00%-125.00%.Safety was good during the trial,with no serious adverse events reported.Conclusion The consistency of in vitro dissolution behaviors and in vivo pharmacokinetic parameters revealed that the quality of generic formulation of Glimepiride was equivalent to the reference formulation,providing a safe and cost-effective alternative for clinical use.

关 键 词：格列美脲片 溶出曲线 生物等效性 一致性评价 

分 类 号：R977.15[医药卫生—药品]