Efficient Nose-to-Lung (N2L) Aerosol Delivery with a Dry Powder Inhaler

Abstract

Purpose: Delivering aerosols to the lungs through the nasal route has a number of advantages, but its use has been limited by high depositional loss in the extrathoracic airways. The objective of this study was to evaluate the nose-to-lung (N2L) delivery of excipient enhanced growth (EEG) formulation aerosols generated with a new inline dry powder inhaler (DPI). The device was also adapted to enable aerosol delivery to a patient simultaneously receiving respiratory support from high flow nasal cannula (HFNC) therapy.

Methods: The inhaler delivered the antibiotic ciprofloxacin, which was formulated as submicrometer combination particles containing a hygroscopic excipient prepared by spray-drying. Nose-to-lung delivery was assessed using in vitro and computational fluid dynamics (CFD) methods in an airway model that continued through the upper tracheobronchial region.

Results: The best performing device contained a 2.3 mm flow control orifice and a 3D rod array with a 3-4-3 rod pattern. Based on in vitro experiments, the emitted dose from the streamlined nasal cannula had a fine particle fraction <5 μm of 95.9% and mass median aerodynamic diameter of 1.4 μm, which was considered ideal for nose-to-lung EEG delivery. With the 2.3-343 device, condensational growth in the airways increased the aerosol size to 2.5-2.7 μm and extrathoracic deposition was <10%. CFD results closely matched the in vitro experiments and predicted that nasal deposition was <2%.

Conclusions: The developed DPI produced high efficiency aerosolization with significant size increase of the aerosol within the airways that can be used to enable nose-to-lung delivery and aerosol administration during HFNC therapy.

Keywords: active dry powder inhaler (DPI) system; enhanced condensational growth (ECG); excipient enhanced growth (EEG); high flow nasal cannula (HFNC); noninvasive ventilation (NIV).

FIG. 1.

Aerosol generation and delivery devices including the (a) inline dry powder inhaler (DPI) with 3D rod array connected to the nasal cannula, (b) cannula for N2L delivery with a single inlet for aerosol administration with ambient room air, and (c) cannula for N2L delivery during HFNC therapy with two inlets allowing for the aerosol and HFNC gas to be administered to separate nostrils. In panels (b) and (c), the dark shading illustrates the streamlined flow passage for the aerosol. The nasal prongs from the cannula device are short and enter the nostrils only several millimeters.

FIG. 2.

The composite airway model employed in the in vitro experiments and CFD simulations composed of a nose-mouth-throat (NMT) geometry, upper tracheobronchial (TB) model, and a lung chamber designed to provide a 1.6–2.0 sec exposure time of the particles to controlled thermodynamic conditions prior to exiting the right angle arm leading to the impactor for size measurement.

FIG. 3.

Illustration of the (a) N2L and (b) N2L during HFNC therapy nasal cannulas positioned in the nostrils. Only the internal flow passages of the cannulas are shown without the exterior support structure.

FIG. 4.

CFD predictions for the 2.3-343-N2L device of (a) particle trajectories colored according to droplet size and (b) deposition fractions and locations with comparisons to in vitro experimental data. In these simulations the flow and thermodynamic conditions were identical to the in vitro experiments (Table 1). Close agreement is observed between the CFD predictions and in vitro results in terms of MMAD exiting the lung chamber and regional deposition fractions.

FIG. 5.

CFD predictions for the 2.3-343-N2L with HFNC device of (a) particle trajectories colored according to droplet size and (b) deposition fractions and locations with comparisons to in vitro experimental data. In these simulations the flow and thermodynamic conditions were identical to the in vitro experiments (Table 1). Close agreement is observed between the CFD predictions and in vitro results in terms of MMAD exiting the lung chamber and regional deposition fractions.