Experimentally Informed Numerical Simulations of Spray Deposition and Runoff Doses in a 10-Day-Old Nose Model

TL;DR

This study uses simulations to understand how different doses of nasal spray affect drug delivery in 10-day-old infants, showing that higher doses lead to significant drug loss.

Contribution

The study introduces a physiology-based simulation model for spray deposition and runoff in neonatal nasal anatomy.

Findings

Higher spray volumes (1.0 and 2.0 mL) caused significant pharyngeal runoff in both supine and 45° inclined positions.

A 0.25 mL spray was fully retained in the nasal passages without runoff.

Runoff percentages increased with larger spray volumes, reaching over 75% for 2.0 mL doses.

Abstract

Background: Intranasal drug delivery is a preferred route for emergency administration of naloxone in opioid overdose due to its rapid onset of action and ease of use. However, limited knowledge exists on the delivery efficiency and safety of nasal sprays in neonates, particularly in life-threatening situations such as coma states where breathing is compromised. This study presents a physiology-based simulation of spray deposition and runoff loss in a 10-day-old infant nose model. Methods: Spray characteristics, including droplet size distribution, exiting velocity, and plume angle, were measured and implemented in ANSYS Fluent droplet tracking model. Naloxone film thickness was measured on ex vivo porcine nasal mucosa at varying angles and used in the Eulerian Wall-Film model. Simulations were conducted in a 10-day-old nose geometry across multiple doses (0.25, 0.50, 1.0, and 2.0 mL) in supine and 45° inclined postures to quantify regional deposition, liquid film translocation, and pharyngeal runoff. Results: While a 0.25 mL spray was fully retained in the nasal passages, higher doses exceeded the mucosal holding capacity and caused significant runoff. Runoff into the pharynx was 18.5% and 10.1% for the spray volume of 0.50 mL in the 45° back tilt and supine positions, respectively. The 1.0 mL spray caused 55.1% and 53.5% runoff in the 45° back tilt and supine positions, while the 2.0 mL spray caused 77.5% and 76.8% runoff in the 45° back tilt and supine positions, respectively. Conclusions: These findings highlight the critical influence of spray volume on drug delivery outcomes in neonates and provide quantitative guidance for optimizing intranasal naloxone administration in emergency pediatric care.

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