Effects of Nozzle Retraction Elimination on Spray Distribution in Middle-Posterior Turbinate Regions: A Comparative Study

Abstract

The standard multi-dose nasal spray pump features an integrated actuator and nozzle, which inevitably causes a retraction of the nozzle tip during application. The retraction stroke is around 5.5 mm and drastically reduces the nozzle's insertion depth, which further affects the initial nasal spray deposition and subsequent translocation, potentially increasing drug wastes and dosimetry variability. To address this issue, we designed a new spray pump that separated the nozzle from the actuator and connected them with a flexible tube, thereby eliminating nozzle retraction during application. The objective of this study is to test the new device's performance in comparison to the conventional nasal pump in terms of spray generation, plume development, and dosimetry distribution. For both devices, the spray droplet size distribution was measured using a laser diffraction particle analyzer. Plume development was recorded with a high-definition camera. Nasal dosimetry was characterized in two transparent nasal cavity casts (normal and decongested) under two breathing conditions (breath-holding and constant inhalation). The nasal formulation was a 0.25% w/v methyl cellulose aqueous solution with a fluorescent dye. For each test case, the temporospatial spray translocation in the nasal cavity was recorded, and the final delivered doses were quantified in five nasal regions. The results indicate minor differences in droplet size distribution between the two devices. The nasal plume from the new device presents a narrower plume angle. The head orientation, the depth at which the nozzle is inserted into the nostril, and the administration angle play crucial roles in determining the initial deposition of nasal sprays as well as the subsequent translocation of the liquid film/droplets. Quantitative measurements of deposition distributions in the nasal models were augmented with visualization recordings to evaluate the delivery enhancements introduced by the new device. With an extension tube, the modified device produced a lower spray output and delivered lower doses in the front, middle, and back turbinate than the conventional nasal pump. However, sprays from the new device were observed to penetrate deeper into the nasal passages, predominantly through the middle-upper meatus. This resulted in consistently enhanced dosing in the middle-upper turbinate regions while at the cost of higher drug loss to the pharynx.

Keywords: actuation; deposition distribution; high-speed imaging; liquid film translocation; nasal spray; nasal valve; particle size distribution; plume development; visualization.

Figure 1

Nasal models and devices: (a) Sectional casts for regional deposition quantification (front nose, turbinate 1 [T1], turbinate 2 [T2], turbinate 3 [T3], and nasopharynx [NP]); (b) Target region (middle and posterior turbinate) outlined in dashed yellow lines; (c) Cross-sectional views of the sectional casts of the two nasal models (M1 and M2); (d) A conventional nasal spray pump (CONV) and a modified nasal spray pump with the nozzle attached via a flexible tube to the pumping mechanism (MOD); (e) Illustration of the nozzle position and spray plumes with and without retraction (red vs. blue).

Figure 2

Characteristics of the 0.25% w/v methylcellulose liquid spray dispensed from both the conventional (CONV) and modified (MOD) devices following a single dose application: (a) Particle size distribution, with mean (μ) and standard deviation (σ) indicated; (b) Images of the liquid spray plume generated by each device; (c) Contact angle of a drop of 0.25% w/v MC aqueous solution on 3D-printed rigid transparent SLA resin; (d) Dynamic viscosity as a function of MC concentration (% w/v) in an aqueous solution.

Figure 3

Liquid deposition within nasal models M1 and M2 at a 22.5° backward head tilt during a breath-hold (i.e., no flow), captured from the lateral and septum sides of each model after one dose of spray application from both devices: (a) CONV; (b) MOD. The target region is outlined in dashed yellow lines. Different arrow colors were used solely to distinguish different regions of interest.

Figure 4

Deposition variation vs. nozzle type (retracting CONV and fixed MOD) in different regions of the nose with a 22.5° back tilt head position and during a breath-hold for nasal models M1 and M2: (a) Front nose; (b) T1; (c) T2; (d) Total deposition.

Figure 5

Liquid deposition within nasal models M1 and M2 at a 45° backward head tilt during a breath-hold, captured from the lateral and septum sides of each model after one dose of spray application from both devices: (a) CONV, and (b) MOD. The target region is outlined in dashed yellow lines. The arrows highlight major differences in deposition.

Figure 6

Deposition variation vs. nozzle type (retracting CONV and fixed MOD) in different regions of the nose with a 45° back tilt head position and during a breath-hold for nasal models M1 and M2: (a) front nose, (b) T1, (c) T2, (d) T3, (e) nasopharynx (NP), and (f) total deposition.

Figure 7

Liquid deposition within nasal models M1 and M2 at a 22.5° backward head tilt and a constant inhalation airflow (16 L/min), captured from the lateral and septum sides of each model after one dose of spray application from both devices: (a) CONV, and (b) MOD. The target region is outlined in dashed yellow lines.

Figure 8

Deposition variation vs. nozzle type (retracting CONV and fixed MOD) in different regions of the nose with a 22.5° back tilt head position and a constant 16 L/min inhalation airflow for nasal models M1 and M2: (a) front nose, (b) T1, (c) T2, (d) T3, and (e) total deposition.

Figure 9

Liquid deposition within nasal models M1 and M2 at a 45° backward head tilt and a constant inhalation airflow (16 L/min), captured from the lateral and septum sides of each model after one dose of spray application from both devices: (a) CONV, and (b) MOD. The target region is outlined in dashed yellow lines.

Figure 10

Deposition variation vs. nozzle type (retracting CONV and fixed MOD) in different regions of the nose with a 45° back tilt head position and a constant 16 L/min inhalation airflow for nasal models M1 and M2: (a) front nose, (b) T1, (c) T2, (d) T3, (e) nasopharynx (NP), and (f) total deposition.

Figure 11

Violin plots of deposited mass in M1 and M2 combined vs. device, head angle, and inhalation scenario (breath-hold [BH] or constant inhalation [Flow]) in the various turbinate sections: (a) T1, and (b) combined T2 and T3.

Figure 12

Time-series visualization of liquid film development and translocation in the M1 model at a 45° backward head tilt and constant inhalation vs. device type: (a) CONV, and (b) MOD. The target region is outlined in dashed yellow lines.