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 pressurised metered dose inhalers containing 15%w/w ethanol and different quantities of non-volatile component (NVC) (drug and glycerol) were evaluated at 25°C and 55°C, using a custom-built heating rig that pre-heated air prior to aerosolisation. Particle size distributions were assessed using an Anderson 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, vapour pressure of the formulation containing HFA 134a and percent NVC. In general, the mass median aerodynamic diameter was proportional to NVC1/3 , 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, post induction 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 bi-modal to mono modal distribution, indicating complex drying kinetics under ambient conditions.