Deposition simulations of realistic dosages in patient-specific airways with two- and four-way coupling

Int J Pharm. 2024 Dec 7:669:125019. doi: 10.1016/j.ijpharm.2024.125019. Online ahead of print.

Abstract

Inhalers spray over 100 million drug particles into the mouth, where a significant portion of the drug may deposit. Understanding how the complex interplay between particle and solid phases influence deposition is crucial for optimising treatments. Existing modelling studies neglect any effect of particle momentum on the fluid (one-way coupling), which may cause poor prediction of forces acting on particles. In this study, we simulate a realistic number of particles (up to 160 million) in a patient-specific geometry. We study the effect of momentum transfer from particles to the fluid (two-way coupling) and particle-particle interactions (four-way coupling) on deposition. We also explore the effect of tracking groups of particles ('parcels') to lower computational cost. Upper airway deposition fraction increased from 0.33 (one-way coupled) to 0.87 with two-way coupling and 10µm particle diameter. Four-way coupling lowers upper airway deposition by approximately 10% at 100µg dosages. We use parcel modelling to study deposition of 4-20µm particles, observing significant influence of two-way coupling in each simulation. These results show that future studies should model realistic dosages for accurate prediction of deposition which may inform clinical decision-making.

Keywords: Computational particle-fluid dynamics; Deposition; Four-way coupling; Image-based model.