Effect of Nasal Inhalation on Drug Particle Deposition and Size Distribution in the Upper Airway: With Soft Mist Inhalers.

Abstract

Delivery of drugs to the lungs is commonly achieved using nasal and/or oral breathing-assisted techniques. The route of inhalation can substantially change the fate of inhaled droplets. The Respimat® Soft Mist™ Inhaler (SMI) is a commercially available efficient inhaler with 40-60% effectiveness. In the present study, we used computational fluid dynamics (CFD) with a custom setup to investigate the effect of a combined oral/nasal inhalation route on the SMI's regional droplet deposition, size distribution, and flow field. Our setup used a modified induction port (MIP) to mimic nasal inhalation inside the human respiratory tract. Six different oral/nasal flow rate ratios inside the MIP were applied (total flow rate of 30l/min). An overall good agreement was achieved between simulation outcomes and in vitro results. Our results confirmed that the combined inhalation route affects the flow field, altering the MIP's droplet deposition and size distribution. The lowest depositional loss, mainly in the mouth area, was observed at oral/nasal flow rate ratios of O/N = 1 and O/N = 2 with 3% and 7.7% values, respectively. Droplets with a 2-5µm diameter range showed the highest droplet mass inside the MIP at all combined flow rates. We observed less intense vortexes followed by a lower level of turbulent kinetic energy at the oral/nasal ratio of 1. Increasing the relative humidity (RH) at oral/nasal flow rate ratios of 0.07, 1, and 14 led to an increase in droplet deposition at the outlet of the MIP.