药学学报, 2021, 56(10): 2669-2675
引用本文:
李苗, 魏宁漪, 郑静, 晏菊姣, 陈路, 卢劲涛, 宁保明. 吸入用布地奈德混悬液的体外雾化特性[J]. 药学学报, 2021, 56(10): 2669-2675.
LI Miao, WEI Ning-yi, ZHENG Jing, YAN Ju-jiao, CHEN Lu, LU Jin-tao, NING Bao-ming. In vitro nebulization characteristics of budesonide suspension for inhalation[J]. Acta Pharmaceutica Sinica, 2021, 56(10): 2669-2675.

吸入用布地奈德混悬液的体外雾化特性
李苗1#, 魏宁漪2#, 郑静2,3, 晏菊姣1, 陈路1, 卢劲涛1, 宁保明2*
1. 武汉药品医疗器械检验所, 国家药品监督管理局药物制剂质量研究与控制重点实验室, 湖北 武汉 430075;
2. 中国食品药品检定研究院, 北京 102629;
3. 中国药科大学药学院, 江苏 南京 211198
摘要:
本文建立了吸入用布地奈德混悬液雾化特性的分析方法并分析其影响因素。通过将不同企业生产的吸入用布地奈德混悬液与不同型号的雾化装置联用,使用呼吸模拟器装置研究递送速率及递送总量;使用新一代撞击器与高效液相色谱法研究空气动力学粒径分布(aerodynamic particle size distribution,APSD)。相同企业样品与不同雾化装置联用后测得的微细粒子剂量(fine particle dose,FPD)、质量中值空气动力学粒径(mass median aerodynamic diameter,MMAD)、递送速率(delivery rate)及递送总量(total drug substance delivered,TDD)均存在差异(P <0.01),该差异是由于雾化装置设计参数不同导致。不同企业样品与相同雾化装置联用后测得的FPD存在差异(P <0.01),这可能是由于混悬液中混悬颗粒粒径等理化性质差异导致。本文方法可用于不同吸入液体制剂在临床上选择递送剂量与微细粒子剂量适宜的雾化装置,也可作为吸入液体制剂仿制药的研发与质量一致性评价研究时选择雾化装置和分析方法的指导。
关键词:    吸入用布地奈德混悬液      空气动力学粒径分布      递送速率      递送总量     
In vitro nebulization characteristics of budesonide suspension for inhalation
LI Miao1#, WEI Ning-yi2#, ZHENG Jing2,3, YAN Ju-jiao1, CHEN Lu1, LU Jin-tao1, NING Bao-ming2*
1. NMPA Key Laboratory for Quality Research and Control of Drug Products, Wuhan Institute for Drug and Medical Device Control, Wuhan 430075, China;
2. National Institutes for Food and Drug Control, Beijing 102629, China;
3. School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
Abstract:
We established in vitro evaluation methods of the nebulization characteristics of budesonide suspension for inhalation and analyzed the influence factors. The delivery rate and total drug substance delivered (TDD) of two manufacturers were determined by using the breath simulator with different nebulizers. The aerodynamic particle size distribution was investigated by next generation impactor (NGI) and HPLC as well. The fine particle dose (FPD), the mass median aerodynamic diameter (MMAD), the delivery rate and TDD results of the same sample with different nebulizers were significantly different (P < 0.01), mainly due to the different design parameters of the nebulizers. The FPD of two samples were significantly different (P < 0.01) by the same nebulizers, probably due to differences in physical and chemical properties differences such as suspension particle size. The analysis method of nebulization characteristics provided in this paper can be used to select the nebulization device with appropriate delivery dose and aerodynamic particle size distribution (APSD) for different inhalation liquid preparations in clinical practice, and can also be used as the guidance for the selection of nebulization device and analysis method in the research and development of generic inhalation liquid preparations and quality consistency evaluation.
Key words:    budesonide suspension for inhalation    aerodynamic particle size distribution    delivery rate    total drug substance delivered   
收稿日期: 2021-03-03
DOI: 10.16438/j.0513-4870.2021-0309
基金项目: 国家市场监督管理总局科技计划项目(2020MK130);中国化学制药工业协会公益项目([2020]43-01).
通讯作者: 宁保明,Tel/Fax:86-10-53851575,E-mail:ningbm@nifdc.org.cn
Email: ningbm@nifdc.org.cn
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