药学学报, 2018, 53(9): 1545-1550
引用本文:
唐艳, 何远志, 伍丽, 张柳, 郭涛, 吴文婷, 荆广会, 殷宪振, 朱卫丰, 张继稳. 利用热熔特征检出混合粉体中目标成分粒径及其分布[J]. 药学学报, 2018, 53(9): 1545-1550.
TANG Yan, HE Yuan-zhi, WU Li, ZHANG Liu, GUO Tao, WU Wen-ting, JING Guang-hui, YIN Xian-zhen, ZHU Wei-feng, ZHANG Ji-wen. Determination of particle size and particle size distribution of selected component in mixed powders by its melting characteristics[J]. Acta Pharmaceutica Sinica, 2018, 53(9): 1545-1550.

利用热熔特征检出混合粉体中目标成分粒径及其分布
唐艳1,2, 何远志1,2, 伍丽2, 张柳2, 郭涛2, 吴文婷1, 荆广会3, 殷宪振2,3, 朱卫丰1, 张继稳1,2
1. 江西中医药大学现代中药制剂教育部重点实验室, 江西 南昌 330004;
2. 中国科学院上海药物研究所, 上海 201203;
3. 迪沙药业集团有限公司, 山东 威海 264200
摘要:
药物与辅料的粒径是影响固体制剂质量的重要因素,对原研制剂的逆向工程和仿制药的一致性评价具有重要意义。本文利用可控加热导致微粒熔化前后的显微图像比对,识别目标成分、去除干扰性微粒,建立混合粉体中目标成分微粒粒径及其分布的新方法;以辅料硬脂酸(stearic acid,SA)为研究对象,对具有不规则形态和球形的SA微粒样品,从混合粉体中识别具有熔融特征的SA微粒,得到粒径及其分布;应用同样的方法,分析非诺贝特片剂内的药物微粒粒径及其分布。研究结果表明,经适当的前处理,使得目标微粒与其他微粒在显微视野下充分分离,然后利用热熔特征可以测定混合粉体中目标成分的微粒粒径及其分布。本研究为原研制剂的剖析和仿制药的一致性评价提供可行方法。
关键词:    热熔特征      混合粉体      粒径分布      显微图像      一致性评价     
Determination of particle size and particle size distribution of selected component in mixed powders by its melting characteristics
TANG Yan1,2, HE Yuan-zhi1,2, WU Li2, ZHANG Liu2, GUO Tao2, WU Wen-ting1, JING Guang-hui3, YIN Xian-zhen2,3, ZHU Wei-feng1, ZHANG Ji-wen1,2
1. Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China;
2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China;
3. Disha Pharmaceutical Co., Ltd., Weihai 264200, China
Abstract:
The particle diameters of active pharmaceutical ingredient (API) and excipients are important factors to the quality of preparations and have great significances in the reverse engineering to brand products and the consistent evaluation of generic drugs. In this study, a novel method was established for particle size determination to identify the selected component and eliminate other interferential particles by comparing the microscopic images before and after fusion caused by controllable heating. Stearic acid (SA) particles in irregular and spherical shape were selected as a typical excipient to demonstrate the methodology, which were identified from the mixed particles based upon its melting characteristics to detect their particle sizes as well as the size distributions. In the same approach, the morphology and particle size of fenofibrate particles as API in tablets were analyzed. The results illustrated that the particle diameters and particle size distributions of the selected components in the mixture of particles can be detected via the hot-melting characteristics under the prerequisite of proper pretreatment to separate selected components from other particles in microscopic field. In conclusion, this research provides a practical approach for the reverse engineering purpose to brand products and the consistent evaluation of generic drugs.
Key words:    melting characteristics    mixed powder    particle size distribution    microscopic image    consistent evaluation   
收稿日期: 2018-05-07
DOI: 10.16438/j.0513-4870.2018-0419
基金项目: 国家自然科学基金资助项目(81773645);国家重大科技专项资助项目(2017ZX09101001-006).
通讯作者: 朱卫丰,Tel/Fax:86-21-20231980,E-mail:jwzhang@simm.ac.cn;张继稳,Tel:86-791-7119011,Fax:86-791-7118658,E-mail:zwflady@163.com
Email: jwzhang@simm.ac.cn;zwflady@163.com
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