Designing aerosol size distribution to minimize inter-subject variability of alveolar deposition

Abstract

Lung morphometry has a great influence on the transport and deposition of therapeutic aerosols as well as disease causing micro-organisms. This study aims to establish the relation between aerosol deposition in the alveolar region and parameters determining the lung morphometry. Inter-subject variability in morphometry has been shown to be a cause of poor dosage control in pulmonary drug delivery systems. We employ a computational approach in this study to study the possibility of engineering an aerosol size distribution to minimize the effect of inter-subject variability. The human respiratory system is idealized as a one-dimensional tract, whose cross-section increases as the distance from the trachea increases. The transport of the aerosol is facilitated by inhalation induced alveolar expansion. The numerical model consists of a mass balance equation for the aerosol transport which is coupled with sub-models for deposition by impaction, sedimentation and diffusion. The model has been validated using experimental data from literature on total particle deposition as well as alveolar deposition over a wide range of particle sizes. From the sensitivity analysis it is concluded that distal airway dimensions play a major role in controlling alveolar deposition. For the parametric conditions investigated, model predictions also suggest that particle sizes near 0.01µm and 10µm will result in the least inter-subject variation in alveolar deposition. Finally, we show that total deposition data are not good indicators of subject-to-subject alveolar dosage variation.