10th International Aerosol Conference September 2 - September 7, 2018 America's Center Convention Complex St. Louis, Missouri, USA
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Predicting Local and Systemic Distributions of Inhaled Budesonide Powders using In Vitro Experiments Combined with Numerical Modeling
CONOR A. RUZYCKI, Brynn Murphy, Hafeez Nathoo, Warren H. Finlay, Andrew R. Martin, University of Alberta
Abstract Number: 897 Working Group: Aerosols in Medicine
Abstract Modeling regional deposition of inhaled pharmaceutical aerosols in the respiratory tract provides useful information with which to assess dosing to targeted airways or lung regions. For single breath inhalers such as dry powder inhalers (DPIs) or pressurized metered-dose inhalers (pMDIs), the physics governing aerosol generation and deposition in the mouth and throat is complex, and difficult to capture with existing mathematical models. As such, for these inhalers it is common to estimate extrathoracic deposition experimentally, using idealized or realistic mouth-throat geometries. The size distribution of aerosol penetrating these geometries can then be measured, and used as input to models used to predict regional deposition through the lower airways of the lung.
Recently, predictions of regional deposition fractions have been coupled with models of dispersion, incorporating drug particle dissolution, mucociliary clearance, and absorption, in order to predict the duration of local and systemic exposure to inhaled drugs following aerosol delivery. Such predictions are valuable in assessing whether and for how long therapeutic drug concentrations are achieved in targeted lung regions, and in comparing relative exposures between alternative devices or formulations used to administer the same drug.
In the present work, we examined local and systemic drug concentrations over time following inhalation of budesonide from three different commercial DPIs. Extrathoracic deposition was measured in vitro using the Alberta Idealized Throat (AIT). Particle size distributions penetrating the AIT were measured using a Next Generation Impactor (NGI). The mass of drug captured by the AIT, and on each stage of the NGI, served as input to a regional deposition model used to predict deposited undissolved drug mass in each generation of the lung. Subsequent dissolution of drug in the airway surface liquid (ASL) was modeled as a Nernst-Brunner process. The ASL concentrations of dissolved drug in each airway generation, as well as systemic drug concentrations, were then predicted using a recently-developed compartmental disposition model, incorporating first-order rate constants to describe the competing processes of drug clearance and absorption from the lungs.
Predictions of local and systemic budesonide exposure will be presented and compared for the three DPIs studied. In addition, predicted concentrations of dissolved drug in the ASL will be discussed in relation to in vitro and pharmacokinetic metrics currently used to evaluate equivalency between inhalers.