两厂家恩格列净片的质量对比和生物等效性研究  

Quality comparison and bioequivalence study on two manufacturers of empagliflozin tablet

作　　者：李晓斌[1] 喻明[1] 陈璐 汪楠[1] 王诗婷 胡妮娜 王宁[1] 王华伟[1] 王文萍[1] LI Xiao-bin;YU Ming;CHEN Lu;WANG Nan;WANG Shi-ting;HU Ni-na;WANG Ning;WANG Hua-wei;WANG Wen-ping(The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110032,China)

机构地区：[1]辽宁中医药大学附属医院,沈阳110032

出　　处：《中国新药杂志》2022年第3期292-299,共8页Chinese Journal of New Drugs

基　　金：国家重点研发计划项目基金资助项目(2018YFC1311600);辽宁中医药大学中药临床药理学科建设项目(辽中医校发2016-198);辽宁省“兴辽英才计划”基金资助项目(XLYC1802008);辽宁省中药临床药物代谢动力学重点实验室基金资助项目(辽科发2005-16)。

摘　　要：目的:对市售两厂家生产的恩格列净片进行全面质量对比研究和生物等效性研究。方法:通过对比A厂家注册标准及B厂家执行的进口质量标准,并对两厂家生产的恩格列净片的性状、HPLC鉴别、有关物质、异构体、过氧化杂质、含量均匀度、溶出度、微生物限度、含量测定、晶型实际检测结果进行全面比较。以A厂家恩格列净片为受试药品,B厂家原研恩格列净片作为参比对照药物,以每人25 mg·片^(-1)的给药剂量,分别在空腹和餐后条件下开展生物等效性试验,用HPLC-MS/MS法检测血浆中恩格列净的浓度,评价A厂家与B厂家生产的制剂的生物等效性。结果:A厂家执行的恩格列净片质量标准在有关物质、异构体及溶出度标准控制方面严于B厂家,抽样不同批次恩格列净B厂家存在部分批次的有关物质总和、过氧化杂质含量略高于A厂家。其他指标如性状、HPLC鉴别、溶出度、异构体、含量均匀度、微生物限度、含量等均符合质量标准,两厂家检测结果基本一致。两厂家生产的恩格列净片所含药物晶型一致。生物等效性试验中两厂家血药浓度曲线基本一致,空腹试验和餐后试验中C_(max),AUC_(0-1)和AUC_(0-∞)经对数转换后的几何均值比值的90%置信区间均落在80.00%~125.00%,经统计分析可判断为生物等效。结论:A和B两厂家生产的恩格列净片产品质量均在质量标准规定限度之内,但A厂家执行更为严格的质量标准,批间产品质量控制方面略优于B厂家。人体生物等效性试验结果显示两厂家生产的恩格列净片在质量和疗效方面具有一致性。Objective:To evaluate the quality and bioequivalence of empagliflozin tablets from two manufacturers.Methods:Comparing registration standard of manufacturer A and import quality standard implemented by manufacturer B,properties,HPLC identification,related substances,isomers,peroxide impurity,content uniformity,dissolution,microbial limit,content determination and crystal form of empagliflozin tablets from two manufacturers were compared.The bioequivalence test was carried out after empagliflozin was administered at a dosage of 25 mg/pill/person under fasting and postprandial conditions with empagliflozin tablets of manufacturer A as the test drug and the original empagliflozin tablets of manufacturer B as the reference control drug.The concentrations of empagliflozin in human plasma were detected by HPLC-MS/MS to evaluate the bioequivalence of the formulations produced by manufacturers A and B.Results:the quality standard of empagliflozin tablets implemented by manufacturer A was stricter than that of manufacturer B in terms of relevant substances,isomers and dissolution standards.In a random sample of different batches,the total amount of relevant substances and the content of peroxide impurities in some batches from manufacturer B were slightly higher than that from manufacturer A.Other indicators,such as properties,HPLC identification,dissolution,isomers,content uniformity,microbial limit and content,all meet the quality standards,and the test results of both manufacturers are basically the same.The drug crystal forms in empagliflozin tablets produced by both manufacturers are the same.In bioequivalence test,the blood concentration curves of both manufacturers are basically the same.The 90% confidence intervals of the geometric mean ratios of C_(max),AUC_(0-1) and AUC_(0-∞) after logarithmic conversion in fasting test and postprandial test are 80.00%~125.00%.It can be judged as bioequivalence by statistical analysis.Conclusion:The product qualities of empagliflozin tablets produced by manufacturers A and B a

关 键 词：恩格列净 质量对比 生物等效性 

分 类 号：R912[医药卫生—药学]