Evaluation of enhanced condensational growth (ECG) for controlled respiratory drug delivery in a mouth-throat and upper tracheobronchial model

Abstract

Purpose: The objective of this study is to evaluate the effects of enhanced condensational growth (ECG), as a novel inhalation drug delivery method, on nano-aerosol deposition in a mouth-throat (MT) and upper tracheobronchial (TB) model using in vitro experiments and computational fluid dynamics (CFD) simulations.

Methods: Separate streams of nebulized nano-aerosols and saturated humidified air (39 degrees C-ECG; 25 degrees C-control) were combined as they were introduced into a realistic MT-TB geometry. Aerosol deposition was determined in the MT, generations G0-G2 (trachea-lobar bronchi) and G3-G5 and compared to CFD simulations.

Results: Using ECG conditions, deposition of 560 and 900 nm aerosols was low in the MT region of the MT-TB model. Aerosol drug deposition in the G0-G2 and G3-G5 regions increased due to enhanced condensational growth compared to control. CFD-predicted depositions were generally in good agreement with the experimental values.

Conclusions: The ECG platform appears to offer an effective method of delivering nano-aerosols through the extrathoracic region, with minimal deposition, to the tracheobronchial airways and beyond. Aerosol deposition is then facilitated as enhanced condensational growth increases particle size. Future studies will investigate the effects of physio-chemical drug properties and realistic inhalation profiles on ECG growth characteristics.

Fig. 1

Geometry used to assess enhanced condensational growth (ECG) consisting of a mouth-throat (MT) and tracheobronchial (TB) regions extending down a single path to respiratory generation G5; and b a dual-flow mouthpiece.

Fig. 2

Predicted relative humidity (RH) conditions for the a control (T_aerosol=21°C and T_humidity=25°C) and b ECG (T_aerosol=21°C and T_humidity=39°C) conditions.

Fig. 3

Predicted droplet trajectories contoured according to diameter for the a control (T_aerosol=21°C and T_humidity=25°C) and b ECG (T_aerosol=21°C and T_humidity=39°C) conditions.

Fig. 4

Initial (in vitro measured) and CFD predictions of exiting polydisperse size distributions for the a 560 nm and b 900 nm aerosols.

Fig. 5

Deposition locations and deposition fractions (DF) of drug mass for an initially 560 nm aerosol and a control (T_aerosol=21°C and T_humidity=25°C) vs. b ECG (T_aerosol=21°C and T_humidity=39°C) conditions. Numerically predicted and experimentally determined deposition fractions are shown for each section considered.

Fig. 6

Comparison of in vitro vs. CFD-predicted deposition fractions (DF) of drug mass on a sectional basis for a MMAD_initial=560 nm and T_humidity=25°C, b MMAD_initial= 560 nm and T_humidity=39°C (ECG), c MMAD_initial=900 nm and T_humidity=25°C, and d MMAD_initial=900 nm and T_humidity=39°C (ECG). The aerosol inlet temperature was 21°C in all cases. The error bars denote +/− one standard deviation.

Fig. 7

CFD results of an improved inlet condition with the aerosol and humidity temperatures both at 39°C for the 900 nm aerosol, presented as a the relative humidity field, b droplet trajectories, c exiting size distributions, and d deposition fraction of drug.