Computational insights into dynamic impacts of droplet evaporation and spray release timing on MDI dosimetry in the respiratory tract

Abstract

The effectiveness of metered-dose inhalers (MDIs) in drug delivery is significantly influenced by aerosol dynamics, particularly evaporation and release timing. This study examined the dynamic interactions between these two factors and their impact on deposition patterns in an anatomically realistic airway model. The airflow and thermo-humidity conditions were simulated under spray actuation conditions (i.e., 0.0, 0.7, 1.5, and 2.5 s after inhalation onset). A Lagrangian-based multiphase model, enhanced with adaptive droplet time steps, was used to track droplet evaporation, trajectory, and deposition. Experimentally measured MDI spray properties, including solution composition, polydisperse size distribution, plume angle, and release velocity, were implemented as initial/boundary conditions. Dosimetry was quantified based on both the count and mass of deposited droplets. Results revealed large differences in droplet evaporation between Case 0.0 s and the other three cases. For all release times, evaporation decreased droplet deposition in the mouth and increased deposition in the lower lung, particularly in the two upper lobes. Droplets starting at 5 μm in diameter reduced to 0.93–2.8 μm within 50–200 ms in the respiratory tract, whereas 10 μm droplets shrunk only to 7.5 μm. The spray deposition pattern varies notably depending on whether actuation occurs at the start of inhalation or is delayed by 0.7–2.5 s. This variation stems from slower airflow and extended evaporation time at the beginning of inhalation vs. relatively consistent and quicker evaporation rates in delayed actuation. Correction factors were introduced for delayed actuation cases to align deposition data obtained with and without accounting for droplet evaporation. Because of the initial polydisperse size distribution and subsequent evaporation of spray droplets, mass-based and count-based deposition fraction values in the lower lung differed by one order of magnitude. Further experimental studies are needed to validate predictions regarding droplet behavior and fate in the respiratory tract.