Characterization of respiratory drug delivery with enhanced condensational growth using an individual path model of the entire tracheobronchial airways

Abstract

The objective of this study was to evaluate the delivery of inhaled pharmaceutical aerosols using an enhanced condensational growth (ECG) approach in an airway model extending from the oral cavity to the end of the tracheobronchial (TB) region. The geometry consisted of an elliptical mouth-throat (MT) model, the upper TB airways extending to bifurcation B3, and a subsequent individual path model entering the right lower lobe of the lung. Submicrometer monodisperse aerosols with diameters of 560 and 900 nm were delivered to the mouth inlet under control (25 °C with subsaturated air) or ECG (39 or 42 °C with saturated air) conditions. Flow fields and droplet characteristics were simulated using a computational fluid dynamics model that was previously demonstrated to accurately predict aerosol size growth and deposition. Results indicated that both the control and ECG delivery cases produced very little deposition in the MT and upper TB model (approximately 1%). Under ECG delivery conditions, large size increases of the aerosol droplets were observed resulting in mass median aerodynamic diameters of 2.4-3.3 μm exiting B5. This increase in aerosol size produced an order of magnitude increase in aerosol deposition within the TB airways compared with the controls, with TB deposition efficiencies of approximately 32-46% for ECG conditions. Estimates of downstream pulmonary deposition indicted near full lung retention of the aerosol during ECG delivery. Furthermore, targeting the region of TB deposition by controlling the inlet temperature conditions and initial aerosol size also appeared possible.

FIGURE 1

Geometry used to evaluate the enhanced condensational growth (ECG) delivery of submicrometer aerosols in the mouth-throat (MT) and tracheobronchial (TB) regions extending down a single path to bifurcation 15 (B15) of the right lower lobe. It is noted that B11 extends behind the geometry and is therefore not visible.

FIGURE 2

Computational mesh of the MT–TB airway model.

FIGURE 3

Comparison of aerosol deposition efficiency in the upper TB airways between CFD predictions with the MT–TB geometry considered in this study and the experimental results of Zhou and Cheng for a cast-based replica model.

FIGURE 4

Predicted temperature conditions in the MT–TB airway model for (a) Case 2 and (b) Case 4.

FIGURE 5

Predicted relative humidity (RH) conditions in the MT–TB airway model for (a) Case 2 and (b) Case 4.

FIGURE 6

Predicted trajectories of initially 900 nm monodisperse droplets in the MT–TB model for (a) Case 2, (b) Case 3, and (c) Case 4.

FIGURE 7

CFD predictions of polydisperse size distributions at selected locations in the model for initially 560 and 900 nm monodisperse droplets and (a, b) Case 2, (c, d) Case 3, and (e, f) Case 4 delivery conditions.

FIGURE 8

Mass median aerodynamic diameters (MMAD) starting with the mouth inlet and entering each bifurcation from the trachea (B1) to B15 for initially 560 and 900 nm aerosols and Cases 2–4.

FIGURE 9

Particle deposition locations and regional deposition efficiencies of drug mass for an initially 900 nm aerosol with (a) Case 2 and (b) Case 4 conditions.

FIGURE 10

Comparison of deposition efficiencies (DE) within specific regions for initially (a) 560 nm and (b) 900 nm droplets and Cases 1–4.