Evaluation of nasal spray drug absorption has been challenging because deposited particles are consistently transported away by mucociliary clearance during diffusing through the mucus layer. This study developed a novel approach combining Computational Fluid Dynamics (CFD) techniques with a 1-D mucus diffusion model to better predict nasal spray drug absorption. This integrated CFD-diffusion approach comprised a preliminary simulation of nasal airflow, spray particle injection, followed by analysis of mucociliary clearance and drug solute diffusion through the mucus layer. The spray particle deposition distribution was validated experimentally and numerically, and the mucus velocity field was validated by comparing with previous studies. Total and regional drug absorption for solute radius in the range of 1 − 110nm were investigated. The total drug absorption contributed by the spray particle deposition was calculated. The absorption contribution from particles that deposited on the anterior region was found to increase significantly as the solute radius became larger (diffusion became slower). This was because the particles were consistently moved out of the anterior region, and the delayed absorption ensured more solute to be absorbed by the posterior regions covered with respiratory epithelium. Future improvements in the spray drug absorption model were discussed. The results of this study are aimed at working towards a CFD-based integrated model for evaluating nasal spray bioequivalence.

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Prediction of nasal spray drug absorption influenced by mucociliary clearance

Face masks and respirators are used to filter inhaled air, which may contain airborne droplets and high particulate matter (PM) concentrations. The respirators act as a barrier to the inhaled and exhaled air, which may change the nasal airflow characteristics and air-conditioning function of the nose. This study aims to investigate the nasal airflow dynamics during respiration with and without an N95 respirator driven by airflow through the nasal cavity to assess the effect of the respirator on breathing conditions during respiration. To achieve the objective of this study, transient computational fluid dynamics simulations have been utilized. The nasal geometry was reconstructed from high-resolution Computed Tomography scans of a healthy 25-year-old female subject. The species transport method was used to analyze the airflow, temperature, carbon dioxide (CO2), moisture content (H2O), and temperature distribution within the nasal cavity with and without an N95 respirator during eight consecutive respiration cycles with a tidal volume of 500 ml. The results demonstrated that a respirator caused excessive CO2 inhalation by approximately 7× greater per breath compared with normal breathing. Furthermore, heat and mass transfer in the nasal cavity was reduced, which influences the perception of nasal patency. It is suggested that wearers of high-efficiency masks that have minimal porosity and low air exchange for CO2 regulation should consider the amount of time they wear the mask.

N95 respirator mask breathing leads to excessive carbon dioxide inhalation and reduced heat transfer in a human nasal cavity

The impact of nasal adhesions on airflow and mucosal cooling - A computational fluid dynamics analysis.

Importance of cloud motion and two-way momentum coupling in the transport of pharmaceutical nasal sprays

Along with playing vital roles in pathogen exclusion and immune system priming, the upper airways (UAs) and their microbiota are essential for myriad physiological functions such as conditioning and transferring inhaled air. Dysbiosis, a microbial imbalance, is linked with various diseases and significantly impedes the quality of one’s life. Daily inhaled exposures and/or underlying conditions contribute to adverse changes to the UA microbiota. Such variations in the microbial community exacerbate UA and pulmonary disorders via modulating inflammatory and immune pathways. Hence, exploring the UA microbiota’s role in maintaining homeostasis is imperative. The microbial composition and subsequent relationship with airborne exposures, inflammation, and disease are crucial for strategizing innovating UA diagnostics and therapeutics. The development of a healthy UA microbiota early in life contributes to normal respiratory development and function in the succeeding years. Although different UA cavities present a unique microbial profile, geriatrics have similar microbes across their UAs. This lost community segregation may contribute to inflammation and disease, as it stimulates disadvantageous microbial–microbial and microbial–host interactions. Varying inflammatory profiles are associated with specific microbial compositions, while the same is true for many disease conditions and environmental exposures. A shift in the microbial composition is also detected upon the administration of numerous therapeutics, highlighting other beneficial and adverse side effects. This review examines the role of the UA microbiota in achieving homeostasis, and the impact on the UAs of environmental airborne pollutants, inflammation, and disease.

The Upper Airway Microbiota, Environmental Exposures, Inflammation, and Disease.

Airflow through the nasal cavity exhibits a wide variety of fluid dynamic behaviors due to the intricacy of the nasal geometry The flow is naturally unsteady and perhaps turbulent, despite Computational Fluid Dynamics (CFD) in the literature being assumed as having a steady laminar flow Time-dependent simulations can be used to generate detailed data with the potential to uncover new flow behavior, although they are more computationally intensive than steady-state simulations Furthermore, verification of CFD results has relied on a reported pressure drop (eg, nasal resistance) across the nasal airway although the geometries used are different This study investigated the unsteady nature of inhalation at flow rates of 10 l/min, 15 l/min, 20 l/min, and 30 l/min A scale resolving CFD simulation using a hybrid Reynolds-averaged Navier–Stokes--large eddy simulation model was used and compared with experimental measurements of the pressure distribution and the overall pressure drop in the nasal cavity The experimental results indicated a large pressure drop across the nasal valve and across the nasopharynx, with the latter attributed to a narrow cross-sectional area At a flowrate of 30 l/min, the CFD simulations showed that the anterior half of the nasal cavity displayed dominantly laminar but disturbed flow behavior in the form of velocity fluctuations The posterior half of the nasal cavity displayed turbulent activity, characterized by erratic fluctuating velocities, which was enhanced by the wider cross-sectional areas in the coronal plane At 15 l/min, the flow field was laminar dominant with very little disturbance, confirming a steady-state laminar flow assumption is viable at this flow rate

Pressure distribution and flow dynamics in a nasal airway using a scale resolving simulation

Particle deposition in the paranasal sinuses following endoscopic sinus surgery.

The primary objective of this research was to extract the essential information needed for setting atomization break up models, specifically, the Linear Instability Sheet Atomization (LISA) breakup model, and alternative hollow cone models. A secondary objective was to gain visualization and insight into the atomization break up mechanism caused by the effects of viscosity and surface tension on primary break-up, sheet disintegration, ligament and droplet formation. High speed imaging was used to capture the near-nozzle characteristics for water and drug formulations. This demonstrated more rapid atomization for lower viscosities. Image processing was used to analyze the near-nozzle spray characteristics during the primary break-up of the liquid sheet into ligament formation. Edges of the liquid sheet, spray break-up length, break-up radius, cone angle and dispersion angle were obtained. Spray characteristics pertinent for primary breakup modelling were determined from high speed imaging of multiple spray actuations. The results have established input data for computational modelling involving parametrical analysis of nasal drug delivery.

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Primary break-up and atomization characteristics of a nasal spray

Airflow through the nasal cavity exhibits a wide variety of fluid dynamicsbehaviour due to the intricacy of the nasal geometry. The flow is naturallyunsteady and perhaps turbulent, despite CFD in the literature that assumesa steady laminar flow. Time-dependent simulations can be used to generatedetailed data with the potential to uncover new flow behaviour, although theyare more computationally intensive compared with steady-state simulations. Furthermore, verification of CFD results has relied on reported pressure drop(e.g. nasal resistance) across the nasal airway although the geometries usedare different. This study investigated the unsteady nature of inhalation atflow rates of 10, 15, 20, and 30 L/min. A scale resolving CFD simulationusing a hybrid RANS-LES model was used and compared with experimentalmeasurements of the pressure distribution and the overall pressure drop in thenasal cavity. The experimental results indicated a large pressure drop acrossthe nasal valve, as well as across the nasopharynx with the latter attributedto a narrow cross-sectional area. At a flowrate of 30 L/min, the CFD simula-tions showed that the anterior half of the nasal cavity displayed dominantlylaminar but disturbed flow behaviour in the form of velocity fluctuations. Theposterior half of the nasal cavity displayed turbulent activity, characterised byerratic fluctuating velocities, which was enhanced by the wider cross-sectionalareas in the coronal plane. At 15L/min, the flow field was laminar dominantwith very little disturbance confirming a steady-state laminar flow assumptionis viable at this flow rate.

Kendra Shrestha

Papers

Pressure distribution and flow dynamics in a nasal airway using a scale resolving simulation

Particle deposition in the paranasal sinuses following endoscopic sinus surgery.

Primary break-up and atomization characteristics of a nasal spray

Pressure distribution and flow dynamics in a nasal airway using a scale resolving simulation.

Effects of head tilt on squeeze-bottle nasal irrigation - A computational fluid dynamics study.