Multimodal particle size distributions emitted from HFA-134a solution pressurized metered-dose inhalers

The purpose of this research was to investigate the measurement and in vitro delivery implications of multimodal distributions, occurring near or in the respirable range, emitted from pressurized metered-dose inhalers (pMDIs). Particle size distributions of solution pMDIs containing hydrofluoroalkane-134a (HFA-134a) and ethanol were evaluated using 2 complementary particle-sizing methods: laser diffraction (LD) and cascade impaction (CI). Solution pMDIs were formulated from mixtures of HFA-134a (50%–97.5% wt/wt) and ethanol. A range of propellant concentrations was selected for a range of vapor pressures. The fluorescent probe, Rhodamine B, was included for chemical analysis. The complementary nature of LD and CI allowed identification of 2 dominant particle size modes at 1 and 10 μm or greater. Increasing propellant concentrations resulted in increases in the proportion of the size distributions at the 1-μm mode and also reduced the particle size of the larger droplet population. Despite significant spatial differences and time scales of measurement between the particle-sizing techniques, the fine particle fractions obtained from LD and CI were practically identical. This was consistent with LD experiments, which showed that particle sizes did not decrease with increasing measurement distance, and may be explained by the absence of significant evaporation/disintegration of larger droplets. The fine particle fractions (FPFs) emitted from HFA-134a/ethanol solution pMDI can be predicted on the basis of formulation parameters and is independent of measurement technique. These results highlight the importance of presenting particle size distribution data from complementary particle size techniques.