中国新药杂志

药品加速稳定性模型研究进展

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段丽 ¹^,² , 李娜 ¹^,² , 韩璐 ² , 杜颖 ² , 许卉 ¹ , 谭德讲 ²

中国新药杂志 | 药品稳定性研究专栏 2021,30(21): 1990-1997

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中国新药杂志 |药品稳定性研究专栏 2021 , 30 (21) : 1990 -1997

药品加速稳定性模型研究进展

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段丽¹^,², 李娜¹^,², 韩璐², 杜颖², 许卉¹, 谭德讲²

作者信息

¹烟台大学，烟台　264003

²国家药品监督管理局化学药品质量研究与评价重点实验室，中国食品药品检定研究院，北京　102629

通讯作者:

谭德讲，男，主任技师，主要从事药品质量的技术监管与统计分析应用研究。联系电话：（010）53851581，E-mail：tandj@nifdc.org.cn。

作者简介:

段丽，女，硕士研究生，主要从事药品稳定性及有效期预测方向研究。E-mail：18660581381@163.com。

Progress on the study of drug accelerated stability model

Li DUAN¹^,², Na LI¹^,², Lu HAN², Ying DU², Hui XU¹, De-jiang TAN²

Affiliations

¹Yantai University, Yantai 264003, China

²Key Lab for Quality Research and Evaluation of Chemical Drug, National Medical Products Administration, National Institutes for Food and Drug Control, Beijing 102629, China

出版时间: 2021-11-15

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摘要

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目的：

对药品加速稳定性评估模型的研究进展进行综述，寻找更高效、低成本且预测可靠的评估模型。

方法：

药品的稳定性研究是药物开发过程中必不可少的环节。对目前使用的加速稳定性模型，包括Arrhenius，Waterman和Clancy等提出的经典模型从考虑因素、适用范围的广度、实验周期长短和预测的准确性等方面进行优劣性比较。

结果：

经典的Arrhenius动力学模型只考虑到温度的影响，实验周期需3~6个月甚至更长，适用范围窄，仅对不足50%化学物质的稳定性能做出正确预测；而Waterman和Clancy提出的预测模型综合考虑到温度和湿度2个因素对稳定性的影响，经严格的实验设计后，实验周期仅需2~3周，其中Waterman的模型能拟合近71%的温湿度影响因素的稳定性研究，而Clancy的模型几乎能拟合全部温湿度影响因素的稳定性研究，且对有效期的预测比Waterman的模型准确性更高。

结论：

Clancy模型是目前更高效、低成本且预测可靠的评估模型；但Waterman模型比Clancy模型应用更广泛。

关键词

加速稳定性 / Arrhenius公式 / 数学模型 / 有效期 / 化学动力学 / 化学热力学

Abstract

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Objective:

To review the progress on the study of drug accelerated stability models and search for a more efficient, lower-cost and more reliable model.

Methods:

The study of drug stability is an indispensable step in the process of drug development. The advantages and disadvantages of the currently used accelerated stability models (ASMs), including classical Arrhenius' model, Waterman's model and Clancy's models, are compared from the aspects of factors for consideration, extensiveness of suitable application for drug substances, length of experimental period and accuracy of prediction.

Results:

There is only the effect of temperature which is considered in the classical Arrhenius' model, the experimental period is 3~6 months and even more and the range of application is narrow in this model that only less than 50% of drug substances could be used to predict the stability correctly. The effects of temperature and humidity on stability are taken into account in the Waterman's model and Clancy's models. The experimental period needs only 2~3 weeks, in which nearly 71% of the stability of the temperature and humidity influencing factors could be interpreted by Waterman's model, while almost all of them could be interpreted by Clancy's model, and the accuracy of prediction is higher than that of Waterman's model.

Conclusion:

Clancy's model is more efficient, lower-cost and more reliable model than the current model; but the Waterman model is more widely used than the Clancy model.

Key words

accelerated stability / Arrhenius equation / mathematical model / shelf life / chemical kinetics / chemical thermodynamics

引用本文

段丽, 李娜, 韩璐, 杜颖, 许卉, 谭德讲. 药品加速稳定性模型研究进展. 中国新药杂志, 2021 , 30 (21) : 1990 -1997 .

Li DUAN, Na LI, Lu HAN, Ying DU, Hui XU, De-jiang TAN. Progress on the study of drug accelerated stability model[J]. Chinese Journal of New Drugs, 2021 , 30 (21) : 1990 -1997 .

基金

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中国食品药品检定研究院重点实验室建设项目

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2021年第30卷第21期

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首发时间：2026-10-30
出版时间：2021-11-15

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录用日期：2021-09-08

基金

中国食品药品检定研究院重点实验室建设项目

作者信息

¹烟台大学，烟台　264003

²国家药品监督管理局化学药品质量研究与评价重点实验室，中国食品药品检定研究院，北京　102629

通讯作者:

谭德讲，男，主任技师，主要从事药品质量的技术监管与统计分析应用研究。联系电话：（010）53851581，E-mail：tandj@nifdc.org.cn。

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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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