标准研讨

国产盐酸地芬尼多片与原研制剂的溶出曲线和有关物质比较研究*

展开
  • 广西壮族自治区食品药品检验所, 南宁 530021
第一作者: Tel: (0771)5828448;E-mail: viviamsky@aliyun.com
** Tel: (0771)5828448, E-mail: 553083970@qq. com

收稿日期: 2020-06-30

  网络出版日期: 2024-05-31

基金资助

* 广西重点研发计划(编号: 桂科AB17292049); 广西重点研发计划(编号: 桂科AB18221125); 十三五国家科技专项“重大新药创制”课题(2017ZX09101001)

Study on in vitro consistency evaluation of domestic difenidol hydrochloride tablets by the determination of related substances and dissolution curves*

Expand
  • Guangxi Institute for Food and Drug control, Nanning 530021, China

Received date: 2020-06-30

  Online published: 2024-05-31

摘要

目的: 通过测定国产盐酸地芬尼多片和原研制剂的有关物质和溶出度, 评价国产仿制制剂与原研制剂的质量一致性。方法: 参照《中华人民共和国药典》2015 年版方法进行溶出试验, 用pH 1. 2 盐酸溶液、pH 4. 0 醋酸盐溶液、pH 6. 8 磷酸盐溶液、水4 种溶出介质测定溶出曲线, 分析国产制剂与原研制剂的溶出曲线相似性。借助GastroplusTM 软件结合体外溶出试验结果, 建立盐酸地芬尼多片体内外相关性模型。使用HPLC 法测定有关物质, 以0. 5% 三乙胺(有磷酸调pH 至4. 0)-甲醇(44∶56)为流动相, 测定原研制剂、3批仿制制剂及盐酸地芬尼多原料的已知杂质和未知杂质。结果: 国产仿制制剂的体外溶出行为与原研不相似, 软件分析结果显示体外溶出曲线与软件模拟的体内行为不相符, 体外溶出度测定方法不能反应体内溶出吸收过程。国产仿制制剂中除已知的降解杂质烯化合物来源于原料外, 其他杂质主要来源于辅料, 已知杂质和未知杂质含量均与原研制剂相当。结论: 国产盐酸地芬尼多片工艺水平有待提高, 溶出一致性评价方法有待进一步研究。

本文引用格式

朱荣, 黄丽丽, 朱健萍 . 国产盐酸地芬尼多片与原研制剂的溶出曲线和有关物质比较研究*[J]. 药物分析杂志, 2021 , 41(3) : 501 -507 . DOI: 10.16155/j.0254-1793.2021.03.16

Abstract

Objective: To evaluate the quality consistency of generic preparation and reference preparation by measuring the related substances and dissolution of domestic difenidol hydrochloride tablets and reference preparation. Methods: The dissolution test was carried out according to the method in Chinese Pharmacopoeia (2015). The dissolution curves were determined using four dissolution mediums of(pH 1. 2 hydrochloric acid solution, pH 4. 0 acetate solution, pH 6. 8 phosphate solution and water), and the similarity of dissolution curves between domestic preparation and reference preparation was analyzed. With the help of gastroplustm software and based on in vitro dissolution test results, the correlation model of difenidol hydrochloride tablets in vivo and in vitro was established. HPLC method was used to determine the related substances, with the mobile phase of 0. 5% triethylamine(pH adjusted to 4. 0 with phosphoric acid)-methanol(44: 56), the known impurities and unknown impurities of the reference preparation, 3 batches of generic preparations and the raw materials of difenidol hydrochloride was tested. Rusults: The in vitro dissolution behavior of the domestic generic preparations is not similar to that of the reference preparation. The software analysis results show that the in vitro dissolution curve does not match the in vivo behavior. The in vitro dissolution determination method could not reflect the in vivo dissolution and absorption process. In the domestic generic preparations, the known degradation impurity alkene compound is derived from raw materials, while other impurities were mainly derived from excipient materials. The contents of known impurities and unknown impurities were equivalent to those of the reference preparation. Conclusion: The technology level of domestic difenidol hydrochloride tablets needs to be improved, and the dissolution consistency evaluation method needs to be further studied。

参考文献

[1] 中华人民共和国药典 2015 年版. 二部华人民共和国药典 2015 年版. 二部[S]. 2015: 930
ChP 2015. hP 2015. Vol Ⅱ[S]. 2015: 930
[2] 张凤妹, 王建, 李佳妮. 国内外阿那曲唑片溶出曲线相似性评价及采用GastroplusTM 建立体内外相关性模型的研究[J]. 中国现代应用药学, 2017, 34(9): 1272
ZHANG FM, WANG J, LI JN. Evaluation for the dissolution curve similarity of domestic and overseas anastrozole tablets[J]. Chin J Mod Appl Pharm, 2017, 34(9): 1272
[3] 潘瑞雪, 余方键, 邹文博, 等. 用GastroPlus 软件模拟技术评价头孢地尼胶囊制剂的有效性[J]. 中国新药杂志, 2014, 23(13): 1506
PAN RX, YU WJ, ZOU WB, et al. GastroPlus simulation technology for evaluating the bioequivalence of cefdinir capsules[J]. Chin J New Drugs, 2014, 23(13): 1506
[4] GRBIC S, PAROJICIC J, IBRIC S, et al. In vitro-in vivo correlation for gliclazide immediate-release tablets based on mechanistic absorption simulation[J]. AAPS PHarm Sci Tech, 2011, 12(1): 165
[5] PAROJCIC J, STOJKOVIC A, TAJBER L, et al. Biopharmaceutical character rization of ciprofloxacin HCl-ferrous sulfate interaction[J]. J Pharm Sci, 2011, 100(12): 5174
[6] 王健康, 董晓莉, 乔建忠, 等. 地芬尼多在健康人体内药动学研究[J]. 中国药学杂志, 2009, 44(7): 524
WANG JK, DONG XJ, QIAO JZ, et al. Pharmacokinetics of difenidol in healthy volunteers[J]. Chin Pharm J, 2009, 44(7): 524
[7] 王健康, 董晓莉, 张福成, 等. 地芬尼多口腔崩解片体内代谢探讨[J]. 中国药师, 2010, 13(1): 91
WANG JK, DONG XL, ZHANG FC, et al. Metabolism of difenidol oral cavity disintegration tablet in vivo[J]. China Pharm, 2010, 13(1): 91
[8] 石靖, 许真玉. 口服固体制剂一致性评价处方工艺研究的常见问题分析[J]. 中国新药杂志, 2019, 28(13): 1561
SHI J, XU ZY. Common problems analyses in the formulation and process research on consistency evaluation of oral solid dosage form[J]. Chin J New Drugs, 2019, 28(13): 1561
[9] 杜冠华. 保障药品安全与提高药品质量问题探讨[J]. 医药导报, 2013, 32(2): 135
DU GH. Discussion on guaranteeing drug safety and improving drug quality[J]. Her Med, 2013, 32(2): 135
[10] 金方方, 尹婕, 南楠. 化学口服固体制剂仿制药质量和疗效一致性评价研究思考[J]. 药物分析杂志, 2018, 38(4): 575
JIN FF, YIN J, NAN N. Study on quality and efficacy consistency evaluation of chemical oral solid generic drugs[J]. Chin J Pharm Anal, 2018, 38(4): 575
[11] 魏敏吉, 解健博. 仿制药一致性评价研究相关问题探讨[J]. 国外医药(抗生素分册), 2017, 38(1): 3
WEI MJ, XIE JB. Discussions on the similarity assessment of generic drugs[J]. World Notes Antibiot, 2017, 38(1): 3
[12] 周立春. 仿制药一致性评价中有关物质研究的思考[J]. 药学进展, 2016, 40(12): 924
ZHOU LC. Reflections on the research of related substances in consistency evaluation for generic drugs[J]. Prog Pharm Sci, 2016, 40(12): 924
[13] 杜冠华, 吕扬. 仿制药一致性评价相关药物晶型的问题分析[J]. 医药导报, 2017, 36(6): 593
Du GH, LU Y. Discussion on Polymorphs in the Consistency Assessment of Generic Drugs[J]. Her Med, 2017, 36(6): 593
[14] 王晋, 张汝华, 孙淑英. 尼莫地平多晶型的研究[J]. 药学学报, 1995, 30(6): 443
WANG J, ZHANG RH, SUN SY. Study on the polymorphism of nimodipine[J]. Acta Pharm Sin, 1995, 30(6): 443
[15] 袁恒杰, 陈大为, 刘艳丽, 等. 尼莫地平多晶型家兔体内药动学研究[J]. 中国药学杂志, 2005, 40(8): 609
YUAN HJ, CHEN DW, LIU YL, et al. Study on pharmacokinetics of nimodipine polymorphs in rabbits[J]. Chin Pharm J, 2005, 40(8): 609
文章导航

/