In a recent study posted to the medRxiv* preprint server, a team of researchers proposed a novel approach to improve intranasal sprays used to treat respiratory viral infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.
Study: A model-based approach to improve intranasal sprays for respiratory viral infections. Image Credit: Dmitry Kovalchuk/Shutterstock
The unprecedented global health crisis caused by the coronavirus disease 2019 (COVID-19) pandemic has necessitated the development of efficient drug delivery systems that can effectively treat or provide relief from symptoms of SARS-CoV-2 infections. Nasal sprays are one such tool that provides efficacious drug delivery, which can be optimized for the improved effectiveness of a drug.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
About the study
The present study investigated various factors that improved the efficacy of nasal sprays and proposed a new approach to developing effective nasal drug delivery systems.
In silico upper airway geometries, recreated from computerized tomography (CT) imaging data of two healthy test subjects, were used in this study. Parameters of inhalation from gentle-to-moderate breathing settings were reproduced at 15 L/min and 30 L/min. The lower flow rate of breathing was associated with viscous and laminar steady-state flow physics, while the higher flow rates caused flow separation induced by shear stress. This flow separation was measured using a large eddy simulation (LES) and a kinetic energy transport model. Velocity component residuals and mass continuity were minimized while static pressure at airflow outlets and mass flow rate were stabilized to track converged solutions accurately.
The dynamics of a nasal spray were evaluated against ambient airflow using the Lagrangian frame of inert discrete phase simulations. Transport equations were integrated, and a no-slip boundary condition was implemented for the cavity walls to calculate the localized droplet clustering around the intranasal tissues. The density of the drug formulation was calibrated to 1.5 g/ml while inert drug droplets of diameters ranging from 1 – 24 µm were released at a pace of 3000 droplets per iteration.
To understand the most effective way to use a nasal spray device, digital models used in the study were tilted forward at an angle of 22.5° while the axis of the spray was closely aligned to the lateral nasal wall. The spray bottle was then placed 5 mm into the airspace as recommended by commercials sprayers.
Results
The results showed that a higher deposition of the drug in the nasopharynx was observed when the spray axis was in the direction proposed by the improved use (IU) protocol as compared to the current use (CU) protocol. Changing the direction of the spray axis from CU to IU noted a 100-fold increase in targeted deposition of the drug. For laminar flow inhalation at 15 L/min, the highest nasopharyngeal deposition of 46.5% was observed for 13 µm drug droplets by IU, while a peak deposition of 0.53% was observed for 14 µm drug droplets by CU. According to the IU protocol, the droplet size in the range of approximately 6 – 14 µm allowed targeted nasopharyngeal delivery.
A Pearson’s correlation coefficient greater than 0.5 was noted when percentages of nasopharyngeal deposition by the IU protocol and perturbed spray directions (PD) were compared, indicating a significant degree of linearity between the IU protocol and the PD. The low p-level observed in this comparison showed a noteworthy correlation between nasopharyngeal deposition by the IU protocol and the PD.
The average improvement of IU compared to CU was 2.117 orders of magnitude and a standard deviation of 0.506 orders. Furthermore, on comparing experimental in vitro projections to computational predictions, a difference of less than 5% was observed.
Conclusion
The study findings showed that a droplet size in the range of 6–14 µm was the most effective in improving the inhaled percentage deposition at targeted upper airway sites, which is crucial in treating SARS-like infections. A significant correlation between the IU protocol and the PD results established the versatility of the IU protocol, irrespective of user subjectivities. The negligible difference in the computational and the in vitro data proved the resilient nature of the in silico framework implemented in this study.
The efficacy of the IU protocol over the CU protocol compelled a revision of the current usage instructions for nasal sprays. The researchers believe that next-generation intranasal drug formulations can be optimized using these findings.
*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
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