Comparative Analysis of Sampling Plans for Delivered Dose Uniformity Investigation of Inhalation Aerosol
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,Volume Ⅳ,referred to as the ChP),the European Pharmacopoeia 11.0(Volume Ⅰ,referred to as the EP)/the British Pharmacopoeia 2023(Volume Ⅲ,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 70 µg),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 sampling plans,and the USP has a lower tolerance for products with greater variability compared to the ChP,EP/BP and JX.
inhalation aerosolpharmacopoeiadelivered dose uniformitysampling planoperating characteristic curveMonte Carlo simulation method
万方数据
维普
