Previous in vivo and ex vivo studies have tested nasal sprays with varying head positions to enhance the olfactory delivery; however, such studies often suffered from a lack of quantitative dosimetry in the target region, which relied on the observer's subjective perception of color changes in the endoscopy images. The objective of this study is to test the feasibility of gravitationally driven droplet translocation numerically to enhance the nasal spray dosages in the olfactory region and quantify the intranasal dose distribution in the regions of interest. A computational nasal spray testing platform was developed that included a nasal spray releasing model, an airflow-droplet transport model, and an Eulerian wall film formation/translocation model. The effects of both device-related and administration-related variables on the initial olfactory deposition were studied, including droplet size, velocity, plume angle, spray release position, and orientation. The liquid film formation and translocation after nasal spray applications were simulated for both a standard and a newly proposed delivery system. Results show that the initial droplet deposition in the olfactory region is highly sensitive to the spray plume angle. For the given nasal cavity with a vertex-to-floor head position, a plume angle of 10° with a device orientation of 45° to the nostril delivered the optimal dose to the olfactory region. Liquid wall film translocation enhanced the olfactory dosage by ninefold, compared to the initial olfactory dose, for both the baseline and optimized delivery systems. The optimized delivery system delivered 6.2% of applied sprays to the olfactory region and significantly reduced drug losses in the vestibule. Rheological properties of spray formulations can be explored to harness further the benefits of liquid film translocation in targeted intranasal deliveries.
Keywords: droplet deposition; liquid film translocation; nasal spray; nose-to-brain delivery; olfactory dose; vertex-to-floor position.