酒石酸美托洛尔片仿制与原研的溶出度比较
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摘要
目的对酒石酸美托洛尔片国产仿制药与原研药进行体外溶出度比较,为质量一致性评价提供依据。方法参照中国药典2010版二部酒石酸美托洛尔片的质量标准,选取50mg规格样品,采用4种不同的溶出介质对国内8家企业生产的仿制药和原研药进行体外溶出行为考察,并采用差异因子f_1法、相似因子f_2法和直接比较法来评价仿制药与原研药溶出行为的一致性。结果 8家仿制药溶出行为参差不齐,按直接比较法只有1家仿制药在四种溶出介质中的溶出曲线均与原研药一致,只在两种或一种溶出介质中的溶出曲线与原研药一致的情况较多。结论国内企业生产的酒石酸美托洛尔片仿制药与原研药存在体外溶出行为不一致性,处方、制剂工艺、辅料的选用方面需要进一步研究,以达到仿制药与原研药体外溶出行为一致性和质量一致性。同时,要结合生物等效性试验,对该品种的国产仿制药和原研药的一致性作出综合的评价。
OBJECTIVE Compare dissolution in vitro of generic drugs and reference listed drug of Metoprolol Tartrate Tablets,then give guidance for quality consistency evaluation of geberic drugs and reference listed drug. METHODS Selected test samples of 50 mg dosage,referring to the quality standard of Metoprolol Tartrate Tablets in Chinese Pharmacopoeia( Ver. 2010),4 kinds of dissolution medium were used to determinate dissolution curve in vitro of 8 generic drugs and 1 reference listed drug,then make consistency evaluation of them by dissimilarity factor f_1,similarity factor f_2 and direct comparison method. RESULTS The dissolution of domestic generic drugs was very different between anyone and each other,only 1 generic drug was consistent with reference listed drug in 4kinds of dissolution medium. Most generic drugs were consistent with reference listed drug in 2 or 1 kinds of dissolution medium. CONCLUSION There are some differences between generic drugs and reference listed drug. Prescription,preparation process and selection of accessories of generic drugs need further study to achieve consistency of quality and dissolution. However,biological equivalence tests were needed in order to make comprehensive evaluation of Metoprolol Tartrate Tablets generic drugs.
OBJECTIVE Compare dissolution in vitro of generic drugs and reference listed drug of Metoprolol Tartrate Tablets,then give guidance for quality consistency evaluation of geberic drugs and reference listed drug. METHODS Selected test samples of 50 mg dosage,referring to the quality standard of Metoprolol Tartrate Tablets in Chinese Pharmacopoeia( Ver. 2010),4 kinds of dissolution medium were used to determinate dissolution curve in vitro of 8 generic drugs and 1 reference listed drug,then make consistency evaluation of them by dissimilarity factor f_1,similarity factor f_2 and direct comparison method. RESULTS The dissolution of domestic generic drugs was very different between anyone and each other,only 1 generic drug was consistent with reference listed drug in 4kinds of dissolution medium. Most generic drugs were consistent with reference listed drug in 2 or 1 kinds of dissolution medium. CONCLUSION There are some differences between generic drugs and reference listed drug. Prescription,preparation process and selection of accessories of generic drugs need further study to achieve consistency of quality and dissolution. However,biological equivalence tests were needed in order to make comprehensive evaluation of Metoprolol Tartrate Tablets generic drugs.
引文
[1]KUKIN M.L,MANNINO M.M,FREUDENBERGER R.S,et al.Hemodynamic comparison of twice daily Metoprolol Tartrate with once daily Metoprolol succinate in congestive heart failure.Journal of the American College of Cardiology[J].2000,35(1):45-50.
[2]国家基本药物目录[M].北京:中国医药科技出版社,2013.
[3]马培奇.心血管疾病治疗药物的发展现状及其研发动态[J].中国制药信息,2001,8(17):1-6.
[4]黄健.酒石酸美托洛尔缓释微丸的研究.硕士学位论文[D].中国人民解放军军事医学科学院,2006.
[5]刘玉辉,贾银珠.地高辛血药浓度监测及不良反应[J].工企医刊,2010,23(3):79.
[6]田国强,马武翔,高赛男,等.氯氮平血药浓度和用药剂量、临床疗效及不良反应关系的研究[J].中国医院药学杂志,2006,26(1):102.
[7]王淑静,张国良,王刚,等.酒石酸美托洛尔片溶出曲线的研究[J].中国现代药物应用,2015,9(5):258.
[8]何丽娟,王岳,侯素云,等.酒石酸美托洛尔片制剂工艺及体外释放度研究[J].中国现代药物应用,2015,9(5):263.
[9]谢沐风.解读“口服固体制剂仿制药一致性评价技术手段--多条溶出曲线”[J].中国医药工业杂志,2013,44(4):411.
[10]王静,付良青,关勇彪,等.酒石酸美托洛尔片人体生物利用度和生物等效性研究[J].中国临床药理学与治疗学,2006,11(9):1043.
[11]高玉成,王琸,于淼,等.浅谈溶出度和仿制药质量一致性评价[J].中国新药杂志,2015,24(3):317.
[12]郑洁,陈玉文.日本药品品质再评价工程对我国仿制药一致性评价的借鉴[J].中国药业,2014,23(18):6.
[13]林兰,牛剑钊,宁保明,等.口服固体制剂一致性评价方式与技术相关问题探讨[J].中国药事,2013,27(10):1018.
[14]韩静,张丹,刘会臣.仿制药的生物不等效风险及质量一致性评价[J].中国新药杂志,2014,23(24):2897.
[15]黄浪,伍巧吉.谈原研药与仿制药的不同[J].北方药学,2011,8(8):83.
[16]郁庆华,谢冉行.开展仿制药质量一致性评价的探讨[J].上海医药,2014,35(7):49.
[17]牛剑钊,林兰,张启明.美国和日本溶出曲线相似性判定方法介绍[J].中国药物评价,2013,30(2):67.
[18]JAMES E.Polli,G.Singh Rekhi,LARRY L.Augsburger,et al.Methods to compare dissolution profiles and a rationale for wide dissolution specifications for metoprolol tartrate tablets[J].Journal of Pharmaceutical Sciences,1997,86(6):690.
[19]酒石酸美托洛尔.中国药典2010版[S].二部.北京:化学工业出版社,2010,863.
[20]酒石酸美托洛尔.中国药典2010版[S].二部.北京:化学工业出版社,2010,864.
[21]Metoprolol Tartrate Tablets.U.S.Pharmacopeia 37[M].U.S.Pharmacopeial Convention,2014,3815-3816.
[22]Metoprolol Tartrate Tablets.British Pharmacopeia 2012[M].The Stationery Office,2012,3062-3063.
[23]Metoprolol Tartrate Tablets.Japanese Pharmacopeia 16[M].Pharmaceutical and Medical Device Regulatory Science Society of Japan,2011,1113-1114.
[2]国家基本药物目录[M].北京:中国医药科技出版社,2013.
[3]马培奇.心血管疾病治疗药物的发展现状及其研发动态[J].中国制药信息,2001,8(17):1-6.
[4]黄健.酒石酸美托洛尔缓释微丸的研究.硕士学位论文[D].中国人民解放军军事医学科学院,2006.
[5]刘玉辉,贾银珠.地高辛血药浓度监测及不良反应[J].工企医刊,2010,23(3):79.
[6]田国强,马武翔,高赛男,等.氯氮平血药浓度和用药剂量、临床疗效及不良反应关系的研究[J].中国医院药学杂志,2006,26(1):102.
[7]王淑静,张国良,王刚,等.酒石酸美托洛尔片溶出曲线的研究[J].中国现代药物应用,2015,9(5):258.
[8]何丽娟,王岳,侯素云,等.酒石酸美托洛尔片制剂工艺及体外释放度研究[J].中国现代药物应用,2015,9(5):263.
[9]谢沐风.解读“口服固体制剂仿制药一致性评价技术手段--多条溶出曲线”[J].中国医药工业杂志,2013,44(4):411.
[10]王静,付良青,关勇彪,等.酒石酸美托洛尔片人体生物利用度和生物等效性研究[J].中国临床药理学与治疗学,2006,11(9):1043.
[11]高玉成,王琸,于淼,等.浅谈溶出度和仿制药质量一致性评价[J].中国新药杂志,2015,24(3):317.
[12]郑洁,陈玉文.日本药品品质再评价工程对我国仿制药一致性评价的借鉴[J].中国药业,2014,23(18):6.
[13]林兰,牛剑钊,宁保明,等.口服固体制剂一致性评价方式与技术相关问题探讨[J].中国药事,2013,27(10):1018.
[14]韩静,张丹,刘会臣.仿制药的生物不等效风险及质量一致性评价[J].中国新药杂志,2014,23(24):2897.
[15]黄浪,伍巧吉.谈原研药与仿制药的不同[J].北方药学,2011,8(8):83.
[16]郁庆华,谢冉行.开展仿制药质量一致性评价的探讨[J].上海医药,2014,35(7):49.
[17]牛剑钊,林兰,张启明.美国和日本溶出曲线相似性判定方法介绍[J].中国药物评价,2013,30(2):67.
[18]JAMES E.Polli,G.Singh Rekhi,LARRY L.Augsburger,et al.Methods to compare dissolution profiles and a rationale for wide dissolution specifications for metoprolol tartrate tablets[J].Journal of Pharmaceutical Sciences,1997,86(6):690.
[19]酒石酸美托洛尔.中国药典2010版[S].二部.北京:化学工业出版社,2010,863.
[20]酒石酸美托洛尔.中国药典2010版[S].二部.北京:化学工业出版社,2010,864.
[21]Metoprolol Tartrate Tablets.U.S.Pharmacopeia 37[M].U.S.Pharmacopeial Convention,2014,3815-3816.
[22]Metoprolol Tartrate Tablets.British Pharmacopeia 2012[M].The Stationery Office,2012,3062-3063.
[23]Metoprolol Tartrate Tablets.Japanese Pharmacopeia 16[M].Pharmaceutical and Medical Device Regulatory Science Society of Japan,2011,1113-1114.