Prediction of nasal spray drug absorption influenced by mucociliary clearance

Abstract

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.

Intranasal Zolmitriptan-Loaded Bilosomes with Extended Nasal Mucociliary Transit Time for Direct Nose to Brain Delivery

“…To gain the maximum benefit from the developed intranasal bilosomes, the nasal mucociliary transit time should be extended to allow for more residence of the applied dosage form inside the nasal cavity, improving drug absorption. This can be achieved by loading the developed bilosomes into a mucoadhesive in situ gelling system with high viscosity capable of resisting rapid mucociliary clearance [21,22].…”

Pharmacokinetic-based failure of a detergent virucidal for SARS-COV-2 nasal infections

“…First, nasal surfaces are protected by a mucociliary transport system that clears nasal surfaces of topically deposited agents within 10 min 8, 15,16 . Second, the nasal surfaces exhibit rapid transepithelial absorption of topically applied agents, a property accessed for drug delivery [17][18][19] .…”

“…First, nasal surfaces are protected by a mucociliary transport system that clears nasal surfaces of topically deposited agents within 10 min 8, 15,16 . Second, the nasal surfaces exhibit rapid transepithelial absorption of topically applied agents, a property accessed for drug delivery [17][18][19] . These data suggest that the failure of J&J/S to reduce SARS-CoV-2 titer in the HNE studies re ected primarily the rapid transnasal absorption of the longer chain, more active virucidal components of J&J/S from the lavage uid.…”

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

“…Numerical simulations have been extensively used to investigate nasal spray deliveries [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ]. Kimbell et al [ 26 ] simulated the deposition fractions of 20 and 50 μm droplets in an MRI-based nasal airway model with an inhalation rate of 15 L/min and predicted more than 90% of droplets being deposited in the anterior nose.…”

“…Tong et al [ 23 ] numerically compared the spray nozzle orientation on intranasal dose distribution and recommended a middle spray direction over the upper or lower directions. Shang et al [ 22 ] simulated the nasal spray drug absorption after deposition.…”