Mechanics-guided parametric modeling of intranasal spray devices and formulations for targeted drug delivery to the nasopharynx

Abstract

Improving the efficacy of nasal sprays by enhancing targeted drug delivery to intra-airway tissue sites prone to infection onset is hypothesized to be achievable through an optimization of key device and formulation parameters, such as the sprayed droplet sizes, spray cone angle, and formulation density. This study focuses on the nasopharynx, a primary locus of early viral entry, as the optimal target for intranasal drug delivery. 3D anatomical upper airway geometries reconstructed from high-resolution computed tomography scans were used to numerically evaluate a cone injection approach, with inert particles mimicking the motion of sprayed droplets within an underlying inhaled airflow field. We have considered monodisperse sprayed particles sized between 10 to 50 microns, six densities ranging from 1.0 to 1.5 g/ml for the constituent formulation, and twelve plume angles spanning 1 to 70 degrees subtended by the spray jet at the nozzle position. Large Eddy Simulation-based modeling of the inhaled airflow physics within the anatomical domains was coupled with a Lagrangian particle-tracking framework to derive the drug deposition trend at the nasopharynx. The resulting globally averaged deposition contour map, obtained by interpolating the outcomes for the discrete test parameters, revealed that nasopharyngeal deposition peaked for droplet sizes 25 to 45 microns and plume angles equal to or less than 30 degrees. In addition, the formulation density of 1.0 g/ml yielded the highest mean deposition rate, over the tested range of sprayed particle sizes and plume angles. The findings were experimentally validated through representative physical spray tests conducted in a 3D-printed replica of one of the test geometries and collectively demonstrate that rational optimization of the intranasal spray design is attainable, with substantial enhancement of targeted drug delivery to the nasopharynx.