Many studies suggest limited effectiveness of spray devices for nasal drug delivery due primarily to high deposition and clearance at the front of the nose. Here, nasal spray behavior was studied using experimental measurements and a computational fluid dynamics model of the human nasal passages constructed from magnetic resonance imaging scans of a healthy adult male. Eighteen commercially available nasal sprays were analyzed for spray characteristics using laser diffraction, high-speed video, and high-speed spark photography. Steadystate, inspiratory airflow (15 L/min) and particle transport were simulated under measured spray conditions. Simulated deposition efficiency and spray behavior were consistent with previous experimental studies, two of which used nasal replica molds based on this nasal geometry. Deposition fractions (numbers of deposited particles divided by the number released) of 20- and 50-microm particles exceeded 90% in the anterior part of the nose for most simulated conditions. Predicted particle penetration past the nasal valve improved when (1) the smaller of two particle sizes or the lower of two spray velocities was used, (2) the simulated nozzle was positioned 1.0 rather than 0.5 or 1.5 cm into the nostril, and (3) inspiratory airflow was present rather than absent. Simulations also predicted that delaying the appearance of normal inspiratory airflow more than 1 sec after the release of particles produced results equivalent to cases in which no inspiratory airflow was present. These predictions contribute to more effective design of drug delivery devices through a better understanding of the effects of nasal airflow and spray characteristics on particle transport in the nose.
Certain inhaled chemicals, such as reactive, water-soluble gases, are readily absorbed by the nasal mucosa upon inhalation and may cause damage to the nasal epithelium. Comparisons of the spatial distribution of nasal lesions in laboratory animals exposed to formaldehyde with gas uptake rates predicted by computational models reveal that lesions usually occur in regions of the susceptible epithelium where gas absorption is highest. Since the uptake patterns are influenced by air currents in the nose, interindividual variability in nasal anatomy and ventilation rates due to age, body size, and gender will affect the patterns of gas absorption in humans, potentially putting some age groups at higher risk when exposed to toxic gases. In this study, interhuman variability in the nasal dosimetry of reactive, water-soluble gases was investigated by means of computational fluid dynamics (CFD) models in 5 adults and 2 children, aged 7 and 8 years old. Airflow patterns were investigated for allometrically scaled inhalation rates corresponding to resting breathing. The spatial distribution of uptake at the airway walls was predicted to be nonuniform, with most of the gas being absorbed in the anterior portion of the nasal passages. Under the conditions of these simulations, interhuman variability in dose to the whole nose (mass per time per nasal surface area) due to differences in anatomy and ventilation was predicted to be 1.6-fold among the 7 individuals studied. Children and adults displayed very similar patterns of nasal gas uptake; no significant differences were noted between the two age groups.
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