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Targeted nasal drug delivery can provide improved efficacy for drug formulations to be delivered at high efficacy rates. Some parameters that influence drug delivery have a dependency on the patient's technique of administration and the spray device itself. When the different parameters, each having a specific range of values are combined, the combinatory permutations for studying its effects on particle deposition become large. In this study, we combine six input spray parameters (the spray half-cone angle, the mean spray exit velocity, the breakup length from the nozzle exit, the diameter of the nozzle spray device, the particle size, and the sagittal angle of the spray) with a range of values to produce 384 combinations of spray characteristics. This was repeated for three inhalation flow rates of 20, 40, and 60 L/min. To reduce the computational costs of a full transient Large Eddy Simulation flow field, we create a time-averaged frozen field and perform the time integration of particle trajectories through the flow field to determine the particle deposition in four anatomical regions of the nasal cavity (anterior, middle, olfactory and posterior) for each of the 384 spray field. A sensitivity analysis determined the significance of each input variable on the deposition. It was found the particle size distribution significantly affected deposition in the olfactory and posterior regions, while the spray device insertion angle was significant for deposition in the anterior and middle regions. Five machine learning models were evaluated based on 384 cases and it was found that despite the small sample dataset the simulation data was sufficient to provide accurate machine-learning predictions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Validating numerical models against experimental models of nasal spray deposition is challenging since many aspects must be considered. That being said, it is a critical step in the product development process of nasal spray devices. This work presents the validation process of a nasal deposition model, which demonstrates a high degree of consistency of the numerical model with experimental data when the nasal cavity is segmented into two regions but not into three. Furthermore, by modelling the flow as stationary, the computational cost is drastically reduced while maintaining quality of particle deposition results. Thanks to this reduction, a sensitivity analysis of the numerical model could be performed, consisting of 96 simulations. The objective was to quantify the impact of four inputs: the spray half cone angle, mean spray exit velocity, breakup length from the nozzle exit and the diameter of the nozzle spray device, on the three quantities of interest: the percentage of the accumulated number of particles deposited on the anterior, middle and posterior sections of the nasal cavity. The results of the sensitivity analysis demonstrated that the deposition on anterior and middle sections are sensitive to injection angle and breakup length, and the deposition on posterior section is only, but highly, sensitive to the injection velocity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Deposition of polydisperse particles representing nasal spray application in a human nasal cavity was performed under transient breathing profiles of sniffing, constant flow, and breath hold. The LES turbulence model was used to describe the fluid phase. Particles were introduced into the flow field with initial spray conditions, including spray cone angle, insertion angle, and initial velocity. Since nasal spray atomizer design determines the particle conditions, fifteen particle size distributions were used, each defined by a log-normal distribution with a different volume mean diameter (Dv50). Particle deposition in the anterior region was approximately 80% when Dv50 > 50μm, and this decreased to 45% as Dv50 decreased to 10μ m for constant and sniff breathing conditions. The decrease in anterior deposition was countered with increased deposition in the middle and posterior regions. The significance of increased deposition in the middle region for drug delivery shows there is potential for nasal delivered drugs to reach the highly vascularised mucosal walls in the main nasal passages. For multiple targeted deposition sites, an optimisation equation was introduced where deposition results of any two targeted sites could be combined and a weighting between 0 to 1 was applied to each targeted site, representing the relative importance of each deposition site., Competing Interests: The authors have declared that no competing interests exist.

The dynamics of unsteady flow in the human large airways during a rapid inhalation were investigated using highly detailed large-scale computational fluid dynamics on a subject-specific geometry. The simulations were performed to resolve all the spatial and temporal scales of the flow, thanks to the use of massive computational resources. A highly parallel finite element code was used, running on two supercomputers, solving the transient incompressible Navier-Stokes equations on unstructured meshes. Given that the finest mesh contained 350 million elements, the study sets a precedent for large-scale simulations of the respiratory system, proposing an analysis strategy for mean flow, fluctuations and wall shear stresses on a rapid and short inhalation (a so-called sniff). The geometry used encompasses the exterior face and the airways from the nasal cavity, through the trachea and up to the third lung bifurcation; it was derived from a contrast-enhanced computed tomography (CT) scan of a 48-year-old male. The transient inflow produces complex flows over a wide range of Reynolds numbers (Re). Thanks to the high fidelity simulations, many features involving the flow transition were observed, with the level of turbulence clearly higher in the throat than in the nose. Spectral analysis revealed turbulent characteristics persisting downstream of the glottis, and were captured even with a medium mesh resolution. However a fine mesh resolution was found necessary in the nasal cavity to observe transitional features. This work indicates the potential of large-scale simulations to further understanding of airway physiological mechanics, which is essential to guide clinical diagnosis; better understanding of the flow also has implications for the design of interventions such as aerosol drug delivery., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

High fidelity simulations of expiratory events such as coughing provide the opportunity to predict the fate of the droplets from the turbulent jet cloud produced from a cough. It is well established that droplets carrying infectious pathogens with diameters of 1 – 5 μ m remain suspended in the air for several hours and transported by the air currents over considerable distances (e.g., in meters). This study used a highly resolved mesh to capture the multiphase turbulent buoyant cloud with suspended droplets produced by a cough. The cough droplets' dispersion was subjected to thermal gradients and evaporation and allowed to disperse between two humans standing 2 m apart. A nasal cavity anatomy was included inside the second human to determine the inhaled droplets. Three diameter ranges characterized the droplet cloud, < 5 μ m , which made up 93% of all droplets by number; 5 to 100 μm comprised 3%, and > 100 μ m comprising 4%. The results demonstrated the temporal evolution of the cough event, where a jet is first formed, followed by a thermally driven puff cloud with the latter primarily composed of droplets under 5 μm diameter, moving with a vortex string structure. After the initial cough, the data were interpolated onto a more coarse mesh to allow the simulation to cover ten minutes, equivalent to 150 breathing cycles. We observe that the critical diameter size susceptible to inhalation was 0.5 μ m , although most inhaled droplets after 10 min by the second human were approximately 0.8 μ m. These observations offer insight into the risk of airborne transmission and numerical metrics for modeling and risk assessment. [ABSTRACT FROM AUTHOR]