Experimental and Computational Analysis of pMDI Aerosol Transport in Pediatric Airways: Impact of Inhalation Flow, Mucus Rheology, and Actuation Timing

Effective drug delivery to the lungs of pediatric patients using pressurized metered-dose inhalers (pMDIs) requires a deep understanding of airflow and particle transport within the airways. This study examines airflow patterns and aerosol deposition in a pediatric mouth-throat (MT) model, incorporating a cystic fibrosis (CF) inhalation profile and simulating the presence of a mucus layer. A CT-derived pediatric MT model was 3D printed and integrated into a next-generation impactor (NGI) to evaluate drug deposition at a flow rate of 15 L/min , offering experimental validation of the computational fluid dynamics (CFD) model. Three different boundary conditions were used to represent the mucus layer, with the Eulerian Wall Film (EWF) approach demonstrating the highest accuracy. The study also explored the effects of a non-Newtonian, shear-thinning mucus layer on deposition behaviour. Large Eddy Simulation (LES) was employed to analyze airflow dynamics, while the Discrete Phase Model (DPM) was utilized to simulate particle transport and deposition. Higher flow rates increased wall shear stress, which enhanced shear-driven transport. Morris’s sensitivity analysis identified flow rate as the dominant factor, demonstrating a strong correlation with deposition efficiency ( r _s = 0.87). Furthermore, the presence of shear-thinning mucus reduced secondary flows, induced asymmetric swirling, and increased the minimum particle size exiting the trachea by 60.2%, rising from 0.491 to 0.789 µm compared to Newtonian mucus. Synchronized actuation further achieved the highest delivery efficiency at 46% due to smooth aerosol entrainment during the buildup of the CF inhalation profile. This transient CF profile also resulted in a broader particle size distribution ranging from 0.78 to 20 µm , in comparison to constant flow rates of 7.5 and 15 L/min .