Optimizing dry powder inhaler for laryngopharyngeal reflux: Effects of particle size and breathing technique

Abstract

Dry powder inhalers (DPIs) were designed to treat lung diseases, but are now being repurposed to address laryngopharyngeal reflux, a condition with no effective treatment. This study assessed how particle size and breathing technique affect DPI deposition on the laryngopharynx using computational fluid dynamics (CFD). Time-dependent airflow and particle transport simulations were performed using the $k-\omega$ turbulence model on a 3-dimensional airway model of a healthy adult. Regional doses were estimated for sinusoidal breathing profiles with different durations (short vs. long inhalation) and depths (shallow vs. forceful inhalation). Three DPIs were simulated assuming log-normal particle size distributions with mass median aerodynamic diameters $\left(d_{50}\right)$ of 3 μm (DPI-1), 10 μm (DPI-2), or 50 μm (DPI-3) representing commercially available DPIs (DPI-1 and DPI-3) and a theoretical DPI optimized for laryngopharyngeal deposition (DPI-2). Particle size was the dominant factor with laryngopharyngeal doses of 5.3%, 20.3%, and 2.2% of the emitted dose for DPI-1, DPI-2, and DPI-3, respectively, with a normal inhalation (30L/min, 2s inhalation). Inhalation duration had a negligible impact on laryngopharyngeal dose for DPI-1 (short inhalation: 6.2%, long inhalation: 4.9%), DPI-2 (short inhalation: 20.6%, long inhalation: 20.3%) and DPI-3 (short inhalation: 1.9%, long inhalation: 2.3%). Similarly, inhalation depth had a negligible impact on the laryngopharyngeal dose for DPI-1 (shallow inhalation: 5.3%, medium inhalation: 5.8%, forceful inhalation: 6.5%), DPI-2 (shallow inhalation: 20.3%, medium inhalation: 20.0%, forceful inhalation: 21.4%) and DPI-3 (shallow inhalation: 2.2%, medium inhalation: 2.0%, forceful inhalation: 2.2%). In summary, our simulations suggest that particle size affects the laryngopharyngeal dose more significantly than the breathing technique with a mass median aerodynamic diameter of $d_{50}=10\mu m$ being predicted to maximize drug delivery to the laryngopharynx. Further studies are needed to validate these findings in larger cohorts.