Alyssa Burke | Searcharxiv

arXiv2019

Numerical evaluation of spray position for improved nasal drug delivery

Topical intra-nasal sprays are amongst the most commonly prescribed therapeutic options for sinonasal diseases in humans. However, inconsistency and ambiguity in instructions show a lack of definitive knowledge on best spray use techniques. In this study, we have identified a new usage strategy for nasal sprays available over-the-counter, that registers an average 8-fold improvement in topical delivery of drugs at diseased sites, when compared to prevalent spray techniques. The protocol involves re-orienting the spray axis to harness inertial motion of particulates and has been developed using computational fluid dynamics simulations of respiratory airflow and droplet transport in medical imaging-based digital models. Simulated dose in representative models is validated through in vitro spray measurements in 3D-printed anatomic replicas using the gamma scintigraphy technique. This work breaks new ground in proposing an alternative user-friendly strategy that can significantly enhance topical delivery inside human nose. While these findings can eventually translate into personalized spray usage instructions and hence merit a change in nasal standard-of-care, this study also demonstrates how relatively simple engineering analysis tools can revolutionize everyday healthcare.

physics.med-ph↗

arXiv2018

Comparative Study of Simulated Nebulized and Spray Particle Deposition in Chronic Rhinosinusitis Patients

Introduction: Topical intranasal drugs are widely prescribed for Chronic Rhinosinusitis (CRS), although delivery can vary with device type and droplet size. The study objective was to compare nebulized and sprayed droplet deposition in the paranasal sinuses and ostiomeatal complex (OMC) across multiple droplet sizes in CRS patients using computational fluid dynamics (CFD). Methods: Three-dimensional models of sinonasal cavities were constructed from computed tomography (CT) scans of three subjects with CRS refractory to medical therapy using imaging software. Assuming steady-state inspiratory airflow at resting rate, CFD was used to simulate 1-120 μm sprayed droplet deposition in the left and right sinuses and OMC with spray nozzle positioning as in current nasal spray use instructions. Zero-velocity nebulization simulations were performed for 1-30 μm droplet sizes, maximal sinus and OMC deposition fractions (MSDF) were obtained, and sizes that achieved at least 50% of MSDF were identified. Nebulized MSDF was compared to sprayed droplet deposition. We also validated CFD framework through in vitro experiments. Results: Among nebulized droplet sizes, 11-14 μm droplets achieved at least 50% of MSDF in all six sinonasal cavities. Five of six sinonasal cavities had greater sinus and OMC deposition with nebulized droplets than with sprayed droplets at optimal sizes. Conclusions: Nebulized droplets may target the sinuses and OMC more effectively than sprayed particles at sizes achieving best deposition. Further studies are needed to confirm our preliminary findings. Several commercial nasal nebulizers have average particle sizes outside the optimal nebulized droplet size range found here, suggesting potential for product enhancement.

physics.med-ph↗