Simulation of Spray Deposition in Adults Nasal Airway

• Author / Creator

  Milad Kiaee Darunkola

• The goal of this thesis work was to develop an idealized adult nasal airway geometry capably of mimicking average regional nasal deposition of droplets emitted from pharmaceutical nasal sprays. The first part of this thesis examined regional deposition within the nose for nasal sprays over a large and wide-ranging parameter space by using numerical simulation. A set of seven realistic adult nasal airway geometries was defined based on Computed Tomography (CT) images. Deposition in six regions of each nasal airway geometry (the vestibule, valve, anterior turbinate, posterior turbinate, olfactory, and nasopharynx) was determined for varying particle diameter, spray cone angle, spray release direction, particle injection speed, and particle injection location. Penetration of nasal spray particles through the airway geometries represented unintended lung exposure. Penetration was found to be relatively insensitive to injection velocity, but highly sensitive to particle size. Penetration remained at or above 30% for particles exceeding 10 microns in diameter for several airway geometries studied. Deposition in the turbinates, viewed as desirable for both local and systemic nasal drug delivery, was on average maximized for particles in the range ~20-30 microns in diameter, and for low to zero injection velocity. Similar values of particle diameter and injection velocity were found to maximize deposition in the olfactory region, a potential target for nose-to-brain drug delivery. However, olfactory deposition was highly variable between airway geometries, with maximum olfactory deposition ranging over two orders of magnitude between geometries. This variability is an obstacle to overcome if consistent dosing between subjects is to be achieved for nose-to-brain drug delivery.
  These simulation results were then used to establish target values of regional deposition for the idealized geometry. Characteristic geometric features observed to be common to all the realistic nasal airway geometries studied were extracted and included in the idealized geometry. Additional geometric features and size scaling were explored at various stages of the project, in order to enhance deposition in specific regions based on the results of simulations done in earlier versions of the geometry. In total, more than hundred thousand of simulation cases were conducted across a range of particle parameters and geometric shapes in order to reach the final idealized geometry presented herein. The proposed idealized geometry has potential use in the development and testing of nasal drug delivery systems, allowing researchers to estimate in vivo regional nasal deposition patterns using a simple benchtop test apparatus.

• Subjects / Keywords

  • Spray
  • Simulation
  • Nasal
  • Deposition
  • Idealized
  • Particles

• Graduation date

  Fall 2018

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R3DJ58Z39

• License

  Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.