Liquid Film Translocation Significantly Enhances Nasal Spray Delivery to Olfactory Region: A Numerical Simulation Study

Abstract

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.

Nasally inhaled therapeutics and vaccination for COVID‐19: Developments and challenges

“…Even for a given device and administration orientation, the drug distribution can vary when different dosages of nasal sprays are applied because of the liquid film translocation. 57 …”

“…Our knowledge of the transient deposition pattern for nasal sprays, however, is still limited at this moment. 57 Further investigations are needed to evaluate the liquid film formation and translocations for different sprays and with different doses.…”

Importance of Spray–Wall Interaction and Post-Deposition Liquid Motion in the Transport and Delivery of Pharmaceutical Nasal Sprays

“…In vitro testing using realistic nasal airway geometries may also help to understand the geometrical factors influencing drug delivery to different regions of the nose [ 7 , 11 , 13 , 14 , 16 , 18 , 19 , 20 , 22 , 39 , 40 , 41 , 42 , 43 ]. In silico testing using computational fluid dynamics (CFD) simulations can provide detailed information on device performance and nasal deposition, and CFD models combined with pharmacokinetic models can provide additional information on systemic drug plasma concentration, while limiting time and cost associated with the testing [ 5 , 9 , 24 , 25 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ].…”

“…In this in vitro study, the liquid spreading was determined using water-sensitive gel, which highlighted post-deposition liquid motion over time. Si et al [ 50 ] computationally demonstrated nasal spray drug delivery to the upper nasal regions using gravity-driven translocation of the deposited spray liquid for a subject in a head-down position relative to gravity. Similarly, Inthavong et al [ 62 ] computationally showed liquid motion on the nasal surface during nasal saline irrigation using a squeeze bottle.…”

Olfactory Drug Aerosol Delivery with Acoustic Radiation

“…However, precise targeting of drugs to the olfactory region (i.e., the first stage in Figure 1 b) has been proven to be highly challenging, as there is no linear pathway from the nostrils to this region [ 20 , 21 ]. With standard intranasal delivery devices, most medications targeting the olfactory region will be filtered out in the front nose and turbinates [ 22 , 23 ].…”