中国新药杂志

计算机模拟技术与平行人工膜渗透模型在富马酸比索洛尔片生物等效性豁免研究中的应用

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郭志渊 ¹ , 谢华 ¹ , 雍子宜 ² , 唐敏 ³ , 袁军 ¹

中国新药杂志 | 重大新药创制专项巡礼 2021,30(6): 507-513

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中国新药杂志 |重大新药创制专项巡礼 2021 , 30 (6) : 507 -513

计算机模拟技术与平行人工膜渗透模型在富马酸比索洛尔片生物等效性豁免研究中的应用

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郭志渊¹, 谢华¹, 雍子宜², 唐敏³, 袁军¹

作者信息

¹四川省食品药品检验检测院，成都　611731

²成都医学院，成都　610500

³四川大学华西药学院，成都　610041

作者简介:

郭志渊，女，大学本科，主要从事药物分析及质量控制研究。E-mail：410616402@qq.com。

Application of computer simulations and parallel artificial membrane permeability assay in the biowaiver study of bisoprol fumarate tablets

Zhi-yuan GUO¹, Hua XIE¹, Zi-yi YONG², Min TANG³, Jun YUAN¹

Affiliations

¹Sichuan Institute for Food and Drug Control, Chengdu 611731, China

²Chengdu Medical College, Chengdu 610500, China

³West China School of Pharmacy, Sichuan University, Chengdu 610041, China

出版时间: 2021-03-30

文章导航

摘要

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目的：

采用计算机模拟技术结合平行人工膜渗透模型（the parallel artificial membrane permeability assay，PAMPA），指导国产富马酸比索洛尔片生物等效性豁免的研究。

方法：

首先利用DDDplus^TM软件评估富马酸比索洛尔片中主成分（active pharmaceutical ingredient，API）及辅料的物理参数对其溶出行为的影响；第2步采用Gastroplus^TM软件的群体模拟实验，模拟药物在体内具有不同释放速率（t_85%=15~120 min）时的体内吸收情况，计算出不影响生物等效性的释放速率范围；第3步测定国产富马酸比索洛尔片、富马酸比索洛尔原料、参比制剂的膜渗透曲线，评估辅料对渗透速率的影响，预测其生物等效性。

结果：

DDDplus^TM模拟结果显示主成分的粒径、各辅料的量和粒径发生变化时，富马酸比索洛尔片的体外溶出行为未发生变化；群体模拟结果显示该药物只要在90 min内完全溶出就能满足与参比制剂生物等效；在空腹肠模拟液中，膜渗透速率曲线显示辅料不影响药物的膜渗透，受试制剂与参比制剂渗透速率基本一致，ρ_max和AUC_0→t无明显差异。

结论：

计算机模拟技术和平行人工膜渗透模型的结果能为富马酸比索洛尔片的生物等效性豁免提供数据支撑。

关键词

富马酸比索洛尔 / 计算机模拟技术 / 平行人工膜渗透模型 / 生物等效性

Abstract

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Objective:

To evaluate the biowaiver of domestic bisoprolol fumarate tablets using computer simulations and parallel artificial membrane permeability assay (PAMPA).

Methods:

First, DDDplus^TM software was used to evaluated the effects of physical parameters of API and excipients on dissolution behavior of bisoprolol fumarate tablets. Second, population simulation using Gastroplus^TM software was used to predict the absorption behavior of the drug with different release rates (t_85%=15~120 min) and obtain the release rate range which had no effect on bioequivalence. Third, the membrane permeation curves of domestic bisoprolol fumarate tablets, bisoprolol fumarate raw material and reference preparation were determined to evaluate the influence of excipients on permeation rate and predict their bioequivalence.

Results:

The results of DDDplus^TM simulation indicated that the in vitro dissolution behavior of bisoprolol fumarate tablets did not change when the particle size of API and excipients, or the amount of excipients, or the particle size of excipients changed. The results of population simulation revealed that the drug preparation could be bioequivalent to the reference preparation as long as it was completely dissolved in 90 minutes. In the jejunum model solution, the membrane permeation rate curve showed that excipients did not affect the membrane permeation behavior of the drug, and the test preparation is bioequivalent with the reference preparation. There was no significant difference in ρ_max and AUC_0→t.

Conclusion:

The application of computer simulations and PAMPA can provide evidence for the biowaiver study of bisoprolol fumarate tablets.

Key words

bisoprolol fumarate / computer simulations / parallel artificial membrane permeability assay / bioequivalence

引用本文

郭志渊, 谢华, 雍子宜, 唐敏, 袁军. 计算机模拟技术与平行人工膜渗透模型在富马酸比索洛尔片生物等效性豁免研究中的应用. 中国新药杂志, 2021 , 30 (6) : 507 -513 .

Zhi-yuan GUO, Hua XIE, Zi-yi YONG, Min TANG, Jun YUAN. Application of computer simulations and parallel artificial membrane permeability assay in the biowaiver study of bisoprol fumarate tablets[J]. Chinese Journal of New Drugs, 2021 , 30 (6) : 507 -513 .

基金

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国家“重大新药创制”科技重大专项资助项目(2017ZX09101001)
四川省科技厅资助项目(2018SZ0001-02)

参考文献

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文献

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参考文献引证文献

排序方式：

[1]

黄峻. 《β受体阻滞剂在心血管疾病中应用的专家共识》精要[J]. 中华高血压杂志, 2011, 19(2): 109-111.

[2]

RAMIREZ E, LAOSA O, GUERRA P, et al. Acceptability and characteristics of 124 human bioequivalence studies with active substances classified according to the Biopharmaceutic Classification System[J]. Br J Clin Pharmacol, 2010, 70(5): 694-702.

[3]

HORIKIRI Y, SUZUKI T, MIZOBE M. Pharmacokinetics and metabolism of bisoprolol enantiomers in humans[J]. J Pharm Sci, 1998, 87(3): 289-294.

[4]

FDA. Guidance for Industry: Waiver on In Vivo Bioavailability and Bioequivalence Studies for Immediate-Release Solid Oral Dosage Forms Based on a Biopharmaceutics Classification System[EB/OL]. (2017-12) [2018-02-03]. https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM070246.pdf.

[5]

OKUMU A, DIMASO M, LÖBENBERG R. Computer simulations using GastroPlus^TM to justify a biowaiver for etoricoxib solid oral drug products[J]. Eur J Pharm Biopharm, 2009, 72(1): 91-98.

[6]

KOVACEVIC I, PAROJCIC J, HOMSEK I, et al. Justification of biowaiver for carbamazepine, a low soluble high permeable compound, in solid dosage forms based on IVIVC and gastrointestinal simulation[J]. Mol Pharm, 2009, 6(1): 40-47.

[7]

WEI H, DALTON C, DIMASO M, et al. Physicochemical characterization of five glyburide powders: a BCS based approach to predict oral absorption[J]. Eur J Pharm Biopharm, 2008, 69(3): 1046-1056.

[8]

吴一凡, 刘晖, 倪京满. 平行人工膜渗透模型及其应用进展[J]. 药学学报, 2011, 46(8): 890-895.

[9]

KANSY M, AVDEEF A, FISCHER H. Advances in screening for membrane permeability: high-resolution PAMPA for medicinal chemists[J]. Drug Discov Today Technol, 2004, 1(4): 349-355.

[10]

王洋洋, 黄聪, 王彩君, 等. 基于平行人工膜渗透分析法对药物溶出/吸收仿生系统优化及其药物渗透性评价研究[J]. 药物评价研究, 2019, 42(8): 1544-1550.

[11]

赵海云, 刘广桢, 王松, 等. 基于来氟米特的溶解度、渗透性分析初步预测制剂的生物等效性[J]. 中国药学杂志, 2018, 53(13): 1117-1122.

[12]

王琳, 吴斌, 王铁松, 等. 基于孟鲁司特钠咀嚼片渗透速率分析初步预测制剂的生物等效性[J]. 中国药学杂志, 2019, 54(18): 1511-1514.

[13]

国家药典委员会. 中华人民共和国药典[S]. 2015年版. 二部. 北京: 中国医药科技出版社, 2015: 121.

[14]

潘瑞雪, 高源, 陈万里, 等. 溶出度实验结合计算机模拟技术评价国产阿莫西林胶囊的生物等效性[J]. 药学学报, 2014, 49(8): 1155-1161.

[15]

TUTUNJI MF, IBRAHIM HM, KHABBAS MH, et al. Simultaneous determination of bisoprolol and hydrochlorothiazide in human plasma by HPLC coupled with tandem mass spectrometry[J]. J Chromatogr B, 2009, 877(16-17): 1689-1697.

[16]

GOMENI R. PHARM: an interactive graphic program for individual and population pharmacokinetic parameter estimation[J]. Comput Biol Med, 1984, 14(1): 25-34.

[17]

DRESSMAN JB, AMIDON GL, REPPAS C, et al. Dissolution testing as a prognostic tool for oral drug absorption: immediate release dosage forms[J]. Pharm Res, 1998, 15(1): 11-22.

[18]

LI GF, WANG K, CHEN R, et al. Simulation of the pharmacokinetics of bisoprolol in healthy adults and patients with impaired renal function using whole-body physiologically based pharmacokinetic modeling[J]. Acta Pharmacol Sin, 2012, 33(11): 1359-1371.

[19]

SUSANTO L, SETIAWATI E, YUNAIDI, et al. Bioequivalence study of two formulations of bisoprolol fumarate film-coated tablets in healthy subjects[J]. Drug Des Dev Ther, 2012: 311.

[20]

BUS-KWASNIK K, RUDZKI PJ, KSYCINSKA H, et al. Bioequivalence study of 2.5 Mg film-coated bisoprolol tablets in healthy volunteers[J]. Kardiol Pol, 2017, 75(1): 48-54.

2021年第30卷第6期

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首发时间：2026-10-29
出版时间：2021-03-30

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录用日期：2020-07-26

基金

国家“重大新药创制”科技重大专项资助项目(2017ZX09101001)

四川省科技厅资助项目(2018SZ0001-02)

作者信息

¹四川省食品药品检验检测院，成都　611731

²成都医学院，成都　610500

³四川大学华西药学院，成都　610041

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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