Plume Geometry Matters: Investigating the Contribution of Mass-Based Plume Geometry to Aerosol Delivery Efficiency in...

To improve the performance of pressurized metered dose inhalers (pMDIs) a better mechanistic understanding of early deposition within the device and upper airways is needed to move toward more efficient inhalation therapies. The present work aimed to address the longstanding gap between plume geometry (PG) measurements and pulmonary drug delivery by evaluating PG with the Plume Induction Port Evaluator (PIPE), a mass-based method that characterizes plume angles under flow and within a restricted geometry. Three Rhodamine B solution pMDI formulations containing 2.49, 9.99, and 19.99% ethanol were evaluated at 5, 25, and 37 °C. PG was characterized by high-speed laser imaging (HSLI, 0 L/min) and by PIPE connected to a Next Generation Impactor (NGI, 30 L/min). Formulation vapor pressure, droplet size by laser diffraction, aerodynamic particle size by cascade impaction, early deposition, fine particle fraction (FPF), and respirable fraction (RF) were also determined. Deposition patterns within PIPE were log-normally distributed and consistently downward oriented, allowing calculation of mass median plume angle (MMPA) under flow. HSLI and MMPA showed opposite responses to formulation vapor pressure, where higher vapor pressure produced narrower optical PG but wider mass-based plume angles. A multivariable model incorporating MMPA, volume median diameter, formulation vapor pressure, and the MMPA × pressure interaction predicted RF with strong agreement (R² = 0.919). These results show that early deposition in pMDIs is not governed by particle size alone, but also by plume trajectory under inhalation flow.