药物溶出试验中桨法的改进及效果初步评价

李琰, 吴恒乾, 王正平, 李素叶, 韩军,

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主办：上海医药工业研究院
　　　中国药学会
　　　中国化学制药工业协会
ISSN 1001-8255   CN 31-1243/R   ZYGZEA
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中国医药工业杂志
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中国医药工业杂志 ›› 2024, Vol. 55 ›› Issue (10) : 1390-1398. DOI: 10.16522/j.cnki.cjph.2024.10.011
研究论文

药物溶出试验中桨法的改进及效果初步评价

  • 李琰1，吴恒乾2，王正平1,3，李素叶4，韩军1,3*
作者信息 +

Improvement and Preliminary Evaluation of Paddle Method in Drug Dissolution Test

  • LI Yan1, WU Hengqian2, WANG Zhengping1,3, LI Suye4, HAN Jun1,3*
Author information +
History +

摘要

桨法装置通常用于药品研发和质量控制，但由于产品落入溶出杯中的沉降位置可能会改变容器底部药物崩解的扩散 范围，故经常受到可重复性和准确性问题的影响，可能无法准确反映药物的释放特性。为了得到更高的重复性，采用在传 统桨法装置的半球形玻璃容器底部添加辅助珠的方式来改良桨法装置。另外，辅助珠的大小可根据不同药物的溶出行为进 行选择。以恩他卡朋(1) 片、达格列净(2) 片和克拉霉素(3) 片作为模型药物对改良桨法装置、传统溶出杯和尖峰溶出杯 进行考察。结果表明，改良桨法装置除了可以根据药物灵活地选择相应的辅助珠外，其获得的药物释放曲线的重复性也更好， 有利于批次间或实验室间溶出曲线的比较。

Abstract

The paddle apparatus is commonly used in both research and development(R&D) and quality control. However, because the settling position of the product after falling into the dissolution vessel may change the diffusion range of drug disintegration at the bottom of the vessel, it is often affected by the problems of reproducibility and accuracy, which may not reflect the drug release characteristics precisely. To achieve better reproducibility, the new modified paddle apparatus was improved by adding auxiliary beads at the bottom of the glass vessel of the paddle apparatus. In addition, the size of the auxiliary beads can be selected according to the dissolution behaviors of different drugs. In this study, entacapone(1) tablets, dapagliflozin(2) tablets and clarithromycin(3) tablets were used as model drugs to Investigate the effects of the improved paddle apparatus, traditional vessel and apex vessel. The results indicated that the improved paddle dissolution vessel could not only select the corresponding auxiliary beads more flexibly according to the drugs, but also obtain better reproducibility of the drug release curves, which was beneficial to the comparison of dissolution results between batches or laboratories.

关键词

溶出装置 / 桨法 / 恩他卡朋 / 达格列净 / 克拉霉素 / 溶出曲线 / 可重复性 / 辅助珠

Key words

dissolution apparatus / paddle method / entacapone / dapagliflozin / clarithromycin / dissolution curve; reproducibility / auxiliary bead

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李琰, 吴恒乾, 王正平, 李素叶, 韩军, . 药物溶出试验中桨法的改进及效果初步评价. 中国医药工业杂志. 2024, 55(10): 1390-1398 https://doi.org/10.16522/j.cnki.cjph.2024.10.011
LI Yan, WU Hengqian, WANG Zhengping, LI Suye, HAN Jun, . Improvement and Preliminary Evaluation of Paddle Method in Drug Dissolution Test. Chinese Journal of Pharmaceuticals. 2024, 55(10): 1390-1398 https://doi.org/10.16522/j.cnki.cjph.2024.10.011

参考文献

[1] 国家药品监督管理局．普通口服固体制剂溶出曲线测定 与比较指导原则[EB/OL]．(2016-03-18)[2024-07-30]． https://www．nmpa．gov．cn/zhuanti/ypqxgg/ggzhcfg/ 20160318210001633．html． 

[2] VAGHELA B, KAYASTHA R, BHATT N, et al． Development and validation of dissolution procedures [J]．J Appl Pharm Sci, 2011, 1(3): 50-56． 

[3] XAVIER P, MATÉO G, SUSANNA A．Mechanistic models for USP2 dissolution apparatus, including fluid hydrodynamics and sedimentation [J]．J Pharm Sci, 2022, 111(1): 185-196． 

[4] BECKETT A H, QUACH T T, KURS G S．Improved hydrodynamics for USP apparatus 2 [J]．Dissolut Technol, 1996, 3(2): 7-18． [5] MANN J, COHEN M J, ABEND A, et al．Stimuli to the revision process: the case for apex vessels stimuli articles do not necessarily reflect the policies of the USPC or the USP council of experts [J]．Dissolut Technol, 2021, 28(4): 6-24． 

[6] 李素叶, 王正平, 吴恒乾, 等．韩氏溶出- 改善利托那韦片 的流体力学和溶出行为[J]．聊城大学学报( 自然科学版), 2021, 34(1): 83-87． 

[7] 韩 军, 王正平． 桨法溶出试验用装置: 中国, 210604597U [P]．2020-05-22． 

[8] 谢沐风．具有区分力的溶出曲线[J]．中国医药工业杂志, 2014, 45(7): 687-689． 

[9] FDA．Dissolution testing and acceptance criteria for immediate release solid oral dosage form drug products containing high solubility drug substances guidance for Industry [EB/OL]．(2018-08-09)[2024-07-30]．https:// www．fda．gov/regulatory-information/search-fda-guidancedocuments． 

[10] NAKAGAWA Y, ITAI S, YOSHIDA T, et al．Physicochemical properties and stability in the acidic solution of a new macrolide antibiotic, clarithromycin, in comparison with erythromycin [J]．Chem Pharm Bull, 1992, 40(3): 725-728． 

[11] BAI G, ARMENANTE P M, PLANK R V, et al． Hydrodynamic investigation of USP dissolution test apparatus Ⅱ [J]．J Pharm Sci, 2007, 96(9): 2327-2349． 

[12] HEALY A M, MCCARTHY L G, GALLAGHER K M, et al．Sensitivity of dissolution rate to location in the paddle dissolution apparatus [J]．J Pharm Pharmacol, 2002, 54(3): 441-444． 

[13] 马 莉, 祝传勇, 何小琳, 等．溶出曲线的常见评价方法 及优劣性探讨[J]．中国新药杂志, 2021, 30(22): 2091-2097． 

[14] KUKURA J, ARRATIA P E, SZALAI E S, et al．Engineering tools for understanding the hydrodynamics of dissolution tests [J]．Drug Dev Ind Pharm, 2003, 29(2): 231-239． 

[15] MIRZA T, JOSHI Y, LIU Y, et al．Evaluation of dissolution hydrodynamics in the USP, peak and flat-bottom vessels using different solubility drugs [J]．Dissolut Technol, 2005, 12(1): 12-52． 

[16] 程晓昆, 仇俊新, 王娅莉, 等．关于体外溶出实验在仿制 药一致性评价中的应用与思考[J]．中国医药工业杂志, 2019, 50(9): 1065-1071．

基金

国家“重大新药创制”科技重大专项(2017ZX09201003-013)、 山东省泰山学者研究基金资助项目(319190201)、山东省抗体药物创新创 业共同体重大科技项目(GTT2111-CYDW-033)
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