吸入制剂微细粒子空气动力学粒径分布评价方法研究

doi:10.19803/j.1672-8629.20230411

摘要/Abstract

摘要： 目的评估吸入制剂的空气动力学粒径分布（APSD）,提高药品质量和安全有效性。方法通过对不同国家药典收载的检测APSD的方法以及相关标准进行比较与总结,用多种计量学参数来表征APSD,通过微细粒子剂量的大小和在总收集剂量中所占的比例作为评估吸入产品的关键指标。结果安德森撞击器（ACI）和新一代撞击器（NGI）是目前应用最广泛也是《美国药典》中所收载的方法,《中华人民共和国药典》又额外收载了玻璃二级撞击器,《欧洲药典》除以上3种装置外还收载了多级液体撞击器。空气动力学质量中值经（MMAD）是控制颗粒在肺部沉积位置的重要变量,几何标准偏差（GSD）表征的是药物颗粒粒度分布曲线形状,越接近于1说明粒度分布越窄。有效数据分析（EDA）中大粒子质量（LPM）与小粒子质量（SPM）的比值以及撞击粒子总质量（ISM）可检测APSD的变化。药物微粒的大小及分布很大程度上决定了粒子在呼吸系统中的沉积部位和沉积量,进而影响药物的疗效。所以若使吸入制剂中的活性药物成分（API）能够经由呼吸系统递送至肺,其气溶胶的空气动力学粒径应在1~5 μm。结论合适的测试方法能够保证吸入产品的质量、安全性和有效性,合理的给药剂量和药物颗粒大小是决定吸入制剂性能的关键指标。不断改进细颗粒的测试方法,深入研究体内外的相关性,能够为吸入产品的进一步研究与开发创造有利条件。

关键词: 吸入制剂, 空气动力学直径, 级联撞击法, 表征方法, 数据分析, 安全性, 一致性评价, 标准

Abstract: Objective To improve the quality, safety, and effectiveness of drugs by evaluating the aerodynamic particle size distribution (APSD) of inhaled formulations. Methods The methods and related standards for detecting APSD specified in different national pharmacopoeias were compared and contrasted. APSD was characterized using multiple econometric parameters. The size of the fine particle dose and its proportion in the total collected dose were used as the key indicators for evaluating inhaled products. Results The Anderson cascade impactor (ACI) and the next generation impactor (NGI) were currently the most widely used and included in the US Pharmacopoeia. The Chinese Pharmacopoeia also included a glass twin impinger while the European Pharmacopoeia also included a multi-stage liquid impactor. The mass median aerodynamic diameter (MMAD) was an important variable to control the deposition position of particles in the lung. The geometric standard deviation (GSD) represented the shape of the drug particle size distribution curve. The closer to 1 the distribution curve, the narrower the distribution of particles. The changes in APSD could be detected by measuring both the ratio of the large particle mass (LPM) to the small particle mass (SPM) and the impactor-sized mass (ISM) in effective data analysis (EDA). The size and distribution of drug particles largely determined the location and amount of particle deposition in the respiratory system, thereby affecting the efficacy of drugs. The delivery of active pharmaceutical ingredients (APIs) in the inhaled formulations to the lungs through the respiratory system required that the aerodynamic particle size of aerosols range from 1 to 5 μm. Conclusion Appropriate testing methods can ensure the quality, safety, and effectiveness of inhaled products. Well-designed dosages and drug particle sizes are the key indicators that determine the performance of inhaled formulations. Therefore, successive improvement of testing methods for fine particles and in-depth research on the correlation between in vitro and in vivo use can facilitate the research and development of inhaled products.

Key words: inhaled products, aerodynamic diameter, cascade impactor, characterization methods, data analysis, safety, consistency evaluation, standard

中图分类号:

R917.4

贾茵茵, 张财树, 周颖, 刘丽, 耿颖, 魏宁漪, 钮思静, 陈华, 许卉. 吸入制剂微细粒子空气动力学粒径分布评价方法研究[J]. 中国药物警戒, 2024, 21(2): 141-146.

JIA Yinyin, ZHANG Caishu, ZHOU Ying, LIU Li, GENG Ying, WEI Ningyi, NIU Sijing, CHEN Hua, XU Hui. Evaluation methods for aerodynamic particle size distribution of fine particles in inhaled products[J]. Chinese Journal of Pharmacovigilance, 2024, 21(2): 141-146.

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