Optimizing Dry Powder Inhalers for Drug Delivery to the Larynx

Commercially available dry powder inhalers (DPIs) with particles of 1-5 μm were originally developed to treat lung diseases. DPIs are under development to treat laryngopharyngeal reflux, but the optimal particle size for laryngeal drug delivery is unknown. Computational fluid and particle dynamics simulations were used to estimate the optimal particle size and release time for optimal laryngeal drug delivery. Transient simulations were performed in a patient-specific model with a sinusoidal breathing profile (breath duration = 4s, mean flow rate = 30L/min). We assumed a log-normal particle size distribution with a geometric standard deviation of 2.0, while the mass median aerodynamic diameter (X₅₀) was varied. The maximal laryngeal dose of 16.0% of the total dose was predicted for the particle release time of 0.25s and X₅₀ = 11.4 µm. For particle release times of 0.50s and 1.0s, the maximal doses were predicted for X₅₀ = 8.8 µm and 7.1 µm, respectively, with laryngeal doses of 6.6% and 6.4%. For comparison, a typical DPI with X₅₀ = 3 µm was predicted to have laryngeal doses of 3.5%, 2.3%, and 3.3% for release times of 0.25s, 0.50s, and 1.0s, respectively. We conclude that X₅₀ = 11.4 µm is the optimal particle size, and 0.25s is the optimal release time to maximize laryngeal drug delivery.