Mucus, airway and plume temperature effects on pMDI-drug delivery in a mouth-throat airway: Experimental and numerical studies

Abstract

Effective pulmonary drug delivery through pressurized-metered dose inhalers (pMDIs) depends on accurately targeting pharmaceutical aerosols to specific lung areas. Achieving this necessitates a comprehensive understanding of airflow dynamics in the airway and particle transport mechanisms.

In this study, a replica of the realistic geometry of the VCU medium-sized mouth-throat (MT) airway was fabricated by rapid prototyping (3D printing) to connect to a next-generation impactor (NGI) setup. The drug concentration deposited in the replica was measured at a constant flow rate of 30 L/min and room temperature using a high-performance liquid chromatography (HPLC) assay. This measurement validated our computational fluid dynamics (CFD) model for simulating particle transport under the same conditions. Large eddy simulation (LES) and discrete phase model (DPM) were employed to model the MT's airflow and particle transport. Using our CFD modeling, we focused on the effects of the temperature distribution of aerosol injection (plume), the influence of inlet air temperature, and the presence of the mucus layer on particle transport and deposition.

Our findings revealed that decreasing the plume temperature from 10 °C to −54 °C reduced deposition by approximately 15%, although increasing the average deposited particle sizes within the MT by about 34.5%. The airflow pattern, affected by different plume temperatures, was the prevalent parameter in particle MT deposition. In contrast, the effect of different air inlet temperatures on deposition was negligible. Additionally, incorporating mucus layer features in CFD modelling could further modify the inhaler's efficiency by up to 11%, depending on the specific conditions like diverse plume temperature (−54 °C–10 °C) and airflow temperature conditions (−15 °C–45 °C).