Abstracto

Investigation of influence factors on particle size measurement with pMDI

Rui Zhang, Xinghan Song, Shuyao Zhan, Junhua Hu, Wen Tan

Laser diffraction (LD) and next generation impactor (NGI) were recommended for measurement of particle size for pressurized metered dose inhaler (pMDI) in Pharmacopoeia. Existing literature had shown that high relative humidity affects in vitro aerosol drug delivery of pMDI. In this study, we investigated the effect of environmental condition (temperature and humidity), flow rate and device temperature on the particle size distribution (PSD) assessment of solution pMDI (Atrovent: Ipratropium Bromide Aerosol, HFA134a) and suspension pMDI (Ventolin: Salbutamol sulfate Aerosol, HFA134a) by LD (Spraytec). We also studied the effect of temperature on the PSD assessment of pMDI by NGI. There was a decrease in particle size with higher humidity or faster flow rate, both for Ventolin and Atrovent. With the environmental temperature increase, the particle sizes of Atrovent were increase. However, the particle sizes of Ventolin were decrease at first and then increase with environmental temperature increase. In addition, with the device temperature increase, the particle sizes were decrease at first and then increase, both for Ventolin and Atrovent. For testing with NGI, mass median aerodynamic diameter (MMAD) was reduced and the fine particle fraction (FPF) increased both for Ventolin and Atrovent when comparing 25°C to 5°C. Therefore, these factors (environmental temperature and humidity, flow rate, and device temperature) had significant influence on the performance of LD or NGI, and should be controlled in the particle size measurement of pMDI.