Aerodynamic particle size analysis of aerosols from pressurized metered-dose inhalers: comparison of Andersen 8-stage cascade impactor, next generation pharmaceutical impactor, and model 3321 Aerodynamic Particle Sizer aerosol spectrometer.

The purpose of this research was to compare three different methods for the aerodynamic assessment of (1) chloroflurocarbon (CFC)--fluticasone propionate (Flovent), (2) CFC-sodium cromoglycate (Intal), and (3) hydrofluoroalkane (HFA)--beclomethasone dipropionate (Qvar) delivered by pressurized metered dose inhaler. Particle size distributions were compared determining mass median aerodynamic diameter (MMAD), geometric standard deviation (GSD), and fine particle fraction <4.7 microm aerodynamic diameter (FPF(<4.7 microm)). Next Generation Pharmaceutical Impactor (NGI)-size distributions for Flovent comprised finer particles than determined by Andersen 8-stage impactor (ACI) (MMAD = 2.0 +/- 0.05 micro m [NGI]; 2.8 +/- 0.07 microm [ACI]); however, FPF(<4.7 microm) by both impactors was in the narrow range 88% to 93%. Size distribution agreement for Intal was better (MMAD = 4.3 +/- 0.19 microm (NGI), 4.2 +/- 0.13 microm (ACI), with FPF(<4.7 microm) ranging from 52% to 60%. The Aerodynamic Particle Sizer (APS) undersized aerosols produced with either formulation (MMAD = 1.8 +/- 0.07 micro m and 3.2 +/- 0.02 micro m for Flovent and Intal, respectively), but values of FPF(<4.7 microm)from the single-stage impactor (SSI) located at the inlet to the APS (82.9% +/- 2.1% [Flovent], 46.4% +/- 2.4% [Intal]) were fairly close to corresponding data from the multi-stage impactors. APS-measured size distributions for Qvar (MMAD = 1.0 +/- 0.03 micro m; FPF(<4.7 micro m)= 96.4% +/- 2.5%), were in fair agreement with both NGI (MMAD = 0.9 +/- 0.03 micro m; FPF(<4.7 microm)= 96.7% +/- 0.7%), and ACI (MMAD = 1.2 +/- 0.02 microm, FPF(<4.7 microm)= 98% +/- 0.5%), but FPF(<4.7 microm) from the SSI (67.1% +/- 4.1%) was lower than expected, based on equivalent data obtained by the other techniques. Particle bounce, incomplete evaporation of volatile constituents and the presence of surfactant particles are factors that may be responsible for discrepancies between the techniques.