Aerosol Dynamics: Applications in Respiratory Drug Delivery Open Access
- Other title
Respiratory Drug Delivery
- Type of item
- Degree grantor
University of Alberta
- Author or creator
- Supervisor and department
Warren H. Finlay (Mechanical Engineering)
- Examining committee member and department
Reinhard Vehring (Mechanical Engineering)
Carlos Lange (Mechanical Engineering)
Department of Mechanical Engineering
- Date accepted
- Graduation date
Doctor of Philosophy
- Degree level
This research comprises four integral parts. Each part focuses on one aspect of the general problem of drug delivery by respiration. The morphological features of human respiratory tract, the dynamics of inhaled pharmaceutical particles, and the mechanics of inhaler devices are particularly taken into consideration.
In the first part, an idealized geometry of the infant nasal airways is developed with the goal of mimicking the average inertial filtration of aerosols by the nasal passages. Paramount geometrical features of 10 previously published nasal replicas of infants aged 3-18 months have been considered in creating the idealized version. A series of overall deposition measurements have been carried out in the idealized replica over a range of particle sizes and breathing patterns. A satisfactory agreement was observed between deposition data for the idealized geometry and those from 10 in vitro subjects.
In the second part, the effect of using helium–oxygen mixture instead of air on hygroscopic size change of inhaled droplets is investigated, with the focus on the favorable transport properties of helium-oxygen. Initially isotonic saline droplets with lognormal size distribution are considered. The effect of mass fraction of the inhaled droplets is highlighted. For high mass fraction, evaporation of smaller droplets saturates the carrier gas, and prevents the evaporation of larger droplets, so hygroscopic effects are believed to be of marginal importance regardless of the carrier gas. In contrast, for medium and low mass fractions, the carrier gas remains less affected by the dispersed phase, and larger droplets are more likely to shrink and pass through the upper airways. In this case, the effects of the physical properties of the carrier gas are more pronounced.
In the third part, the problem of hygroscopic size change of nebulized aerosols is considered, and two approaches to size manipulation of saline droplets are investigated. First, heating the aerosol stream, and second, adding solid sodium-chloride particles to the aerosol stream. The two approaches are aimed at altering the vapor pressure balance between the surface of the droplets and their carrier gas. These processes help the droplets which are larger than optimal to evaporate and shrink, thereby producing desirable droplets for drug delivery, which have less deposition in the extra-thoracic airways and more deposition in the alveolar region of the lung.
In the fourth part, the dynamic equation for the flocculation and upward drift of the suspended drug particles within the canister of a metered dose inhaler is solved numerically. The technique employed is based upon discretizing the particle size distribution using orthogonal collocation on finite elements. This is combined with a finite difference discretization of the canister geometry in the axial direction, and an explicit Runge-Kutta-Fehlberg time marching scheme. The solution represents the particle size distribution as a function of time and position within the canister. The method allows prediction of the effects of the initial conditions and physical properties of the suspension on its dynamic behavior and phase separation.
- 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.
- Citation for previous publication
Javaheri, E., Finlay, W.H., 2013. Size manipulation of hygroscopic saline droplets: Application to respiratory drug delivery. International Journal of Heat and Mass Transfer
67, 690-695.Javaheri, E., Finlay, W.H., 2014. Numerical simulation of flocculation and transport of
suspended particles: Application to metered-dose inhalers. International Journal of
Multiphase Flow 64, 28-34.Javaheri, E., Golshahi, L., Finlay, W., 2013. An idealized geometry that mimics average
infant nasal airway deposition. Journal of Aerosol Science 55, 137-148.Javaheri, E., Shemirani, F.M., Pichelin, M., Katz, I.M., Caillibotte, G., Vehring, R.,
Finlay, W.H., 2013. Deposition modeling of hygroscopic saline aerosols in the human
respiratory tract: Comparison between air and helium-oxygen as carrier gases. Journal
of Aerosol Science 64, 81-93.
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