吸入气雾剂递送剂量均一性考察抽样方案对比分析  

Comparative Analysis of Sampling Plans for Delivered Dose Uniformity Investigation of Inhalation Aerosol

作　　者：晏菊姣 耿颖[2] 魏宁漪[2] 李苗 陈华[2] YAN Jujiao;GENG Ying;WEI Ningyi;LI Miao;CHEN Hua(Wuhan Institute for Drug and Medical Device Control·NMPA Key Laboratory for Quality Research and Control of Drug Products,Wuhan,Hubei,China 430075;National Institutes for Food and Drug Control,Beijing,China 102629)

机构地区：[1]湖北省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

出　　处：《中国药业》2024年第10期81-86,共6页China Pharmaceuticals

基　　金：湖北省药品监督管理局科研项目[20200114]。

摘　　要：目的比较吸入气雾剂递送剂量均一性考察中不同抽样方案的差异。方法汇总2020年版《中国药典(四部)》(简称ChP)、《European Pharmacopoeia 11.0(VolumeⅠ)》(简称EP)/《British Pharmacopoeia 2023(VolumeⅢ)》(简称BP)、《USP-NF online 2024》(简称USP)及我国进口药品注册标准(简称JX)中吸入气雾剂递送剂量均一性考察的抽样方案和判定标准。以硫酸沙丁胺醇吸入气雾剂为例,按ChP及USP抽样方案分别测定4家企业(企业A,B,C,D)6批样品的递送剂量均一性。采用蒙特卡洛模拟法进行数据模拟,并绘制工作特性曲线。结果按ChP抽样方案,样品的递送剂量均一性均符合规定;按USP抽样方案,仅企业C有1批样品的平均递送剂量不符合规定(低于70μg),且与企业D样品比较差异显著(P<0.05)。ChP的工作特性曲线较其他3种判定标准更宽,接受区域更广;EP/BP与JX抽样方案第一阶段接受概率和总接受概率均较接近;USP与JX抽样方案在标准差较小(≤6)时几乎相同,随着标准差的增大,前者的第一阶段接受概率和总接受概率下降程度更显著,在标准差≥10的情况下,其总接受概率<90%。结论不同抽样方案对吸入气雾剂递送剂量均一性的接受概率存在一定差异,USP较ChP,EP/BP,JX对变异较大的产品容忍度更低。Objective To compare the differences of different sampling plans in the delivered dose uniformity investigation of inhalation aerosol.Methods The sampling plans and criteria of investigating the delivered dose uniformity of inhalation aerosol in the Chinese Pharmacopoeia(2020 Edition,VolumeⅣ,referred to as the ChP),the European Pharmacopoeia 11.0(VolumeⅠ,referred to as the EP)/the British Pharmacopoeia 2023(VolumeⅢ,referred to as the BP),the USP-NF online 2024(referred to as the USP)and the China′s import drug registration standards(referred to as the JX)were summarized.Taking Salbutamol Sulfate Inhalation Aerosol as an example,the delivered dose uniformity of six batches of samples from four manufacturers(manufacturers A,B,C,D)was determined based on the sampling plans of the ChP and the USP.The Monte Carlo simulation method was used for data simulation,and the operating characteristic curves were drawn.Results Based on the ChP sampling plan,the delivered dose uniformity of samples all met the regulations.Based on the USP sampling plan,the average delivered dose of only one batch of sample from manufacturer C did not meet the regulations(less than 70μg),and the difference was significant compared to the samples from manufacturer D(P<0.05).The operating characteristic curves of ChP were wider and the acceptance areas were larger than those of other three criteria.The acceptance probability in the first stage and total acceptance probability of EP/BP sampling plan were similar to those of JX sampling plan.The acceptance probability in the first stage and total acceptance probability of USP and JX sampling plans were almost identical when the standard deviation was small(≤6),while as the standard deviation increased,the above two probabilities of the former decreased more significantly,and its total acceptance probability was<90%when the standard deviation was≥10.Conclusion There is a certain difference in the acceptance probability of delivered dose uniformity of inhalation aerosol among different sam

关 键 词：吸入气雾剂 药典 递送剂量均一性 抽样方案 工作特性曲线 蒙特卡洛模拟法 

分 类 号：R917[医药卫生—药物分析学]