The formation of aerosol particles from solution-based pressurized metered dose inhalers and implications of incomplete droplet drying: theoretical and experimental comparison

The aerosol particle size distributions of solution-based pressurized metered dose inhalers containing 15%w/w ethanol and different quantities of nonvolatile component (NVC) (drug and glycerol) were evaluated at 25°C and 55°C, using a custom-built heating rig that preheated air prior to aerosolization. Particle size distributions were assessed using an Andersen cascade impactor and mass-weighted cumulative aerodynamic diameter distributions were compared to a theoretical model that predicts the final size distribution, based on initial droplet size, vapor pressure of the formulation containing HFA 134a and percent NVC. In general, the mass median aerodynamic diameter was proportional to NVC^1/3, with experimental particle size distributions following theoretical values. However, when comparing theoretical vs. experimental data over the range of mass-weighted cumulative aerodynamic diameter distributions between 10 and 90%, the 55°C experimental measurements more closely fitted the theoretical equation when compared to 25°C. This was attributed to incomplete drying of some of the larger initial droplets prior to impaction. Additionally, postinduction port measurements of volumetric size distribution using laser diffraction, showed a reduction in median particle diameter at 55°C, compared to 25°C and a change from bimodal to monomodal distribution, indicating complex drying kinetics under ambient conditions.