Nasal dilation effects on olfactory deposition in unilateral and bi-directional deliveries: In vitro tests and numerical modeling

Publication date: 15 June 2018
Source:European Journal of Pharmaceutical Sciences, Volume 118
Author(s): Jinxiang Xi, Zhaoxuan Wang, Xiuhua April Si, Yue Zhou
The human nose can expand either actively or passively to increase airflow. Nasal dilation may alter drug delivery efficiencies in the nasal airway or olfactory region. However, the dosage enhancement from nasal dilations has not been quantified. The mechanisms underlying the dilation-induced deposition variation are also not clear. This study aims to quantify the nasal dilation effects on drug delivery in the nasal airway and olfactory region using in vitro tests and numerical analysis. Two variants of an existing normal nasal airway model were developed with different levels of airway dilation. Airway dimensions were quantified in terms of hydraulic diameter, cross-sectional area, and surface area to volume ratio. Sectional nose casts were prepared using a 3-D printer for visualizing deposition patterns and quantifying delivered dosages. A well-validated computational fluid-particle dynamics (CFPD) model was utilized to understand the underlying mechanisms in the unilateral and bi-directional deliveries. In vitro tests show that nasal dilation lowered the total dosage in the nose but increased the dosage to the olfactory region in both the unilateral and bi-directional deliveries. Compared to the normal nose with unilateral delivery, nasal dilation enhanced the olfactory deposition by a factor of 2.2, while nasal dilatation with the bi-directional delivery increased by a factor of 4. Complementary numerical analyses revealed the growth of a recirculation zone in the middle meatus of dilated noses, which induced lower pressure and increased ventilation to the upper nose. In bi-directional deliveries, a significantly higher fraction of airflow was ventilated to the upper airway in the outflow side of the nose and contributed to the elevated olfactory dosage. Nasal dilation in combination with the bi-directional delivery is recommended over the conventional unilateral method for olfactory targeting.

Graphical abstract

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