Coupled Discrete Phase and Eulerian Wall Film Models for Drug Deposition Efficacy Analysis in Human Respiratory Airways

Mol Pharm. 2024 Oct 7;21(10):5071-5087. doi: 10.1021/acs.molpharmaceut.4c00482. Epub 2024 Sep 23.

Abstract

The current study explores the effectiveness of drug particle deposition into human respiratory airways to cure various pulmonary-bound ailments. It has been assumed that drug solutions are inhaled in the form of tiny droplets or mist, which after striking create a thin layer along the inner surface of airways where the virus initially resides to infect the human body. A coupled Eulerian wall film (EWF) and discrete phase model (DPM) based simulation approach is used to capture these dynamics. Here, the Lagrangian DPM technique tracks the dynamics of tiny droplets, while the liquid layer formation after striking is captured using the Eulerian thin film approximations or the EWF model. Previous studies in this field primarily employed only the DPM method, which is inadequate to predict the poststriking dynamics of drug layer deposition and their spread to neutralize the respiratory virus. The drug delivery effectiveness is characterized by three different particle sizes, 1, 5, and 10 μm at the inhalation rates of 15, 30, and 60 L per minute (LPM). It has been found that the size of the drug particles significantly influences drug delivery effectiveness. The film thickness increases monotonically with particle sizes and inhalation rates. However, this increase in averaged film thickness is prominent in the range 5 to 10 μm (≈60%) compared to 1 to 5 μm (≈10%) droplet sizes at generation level 4 (G4). The other deposition parameters, e.g., deposition fraction, deposition density, and area coverage) roughly show similar behavior with the increase in droplet sizes. Therefore, it is recommended to vary the droplet sizes between 5 and 10 μm for better deposition effectiveness. The sizes of more than 10 μm mostly stuck into the oral cavity and cannot reach the targeted generations. In contrast, less than 5 μm may reach much deeper generations than the targeted one.

Keywords: Eulerian wall film model; Weibel’s geometry; discrete phase model; drug delivery; inhalation rate; particle deposition.

MeSH terms

  • Administration, Inhalation
  • Aerosols
  • Computer Simulation
  • Drug Delivery Systems / methods
  • Humans
  • Lung / metabolism
  • Models, Biological
  • Particle Size*
  • Respiratory System / drug effects
  • Respiratory System / metabolism
  • Respiratory System / virology

Substances

  • Aerosols