The Influence of Spray Properties on Intranasal Deposition

Abstract

While numerous devices, formulations, and spray characteristics have been shown to influence nasal deposition efficiency, few studies have attempted to identify which of these interacting factors plays the greatest role in nasal spray deposition. The deposition patterns of solutions with a wide range of surface tensions and viscosities were measured using an MRI-derived nasal cavity replica. The resulting spray plumes had angles between 29 degrees and 80 degrees and contained droplet sizes (D(v50)) from 37-157 microm. Each formulation contained rhodamine 590 as a fluorescent marker for detection. Administration angles of 30 degrees , 40 degrees , or 50 degrees above horizontal were tested to investigate the role of user technique on nasal deposition. The amount of spray deposited within specific regions of the nasal cavity was determined by disassembling the replica and measuring the amount of rhodamine retained in each section. Most of the spray droplets were deposited onto the anterior region of the model, but sprays with small plume angles were capable of reaching the turbinate region with deposition efficiencies approaching 90%. Minimal dependence on droplet size, viscosity, or device was observed. Changes in inspiratory flow rate (0-60 L/min) had no significant effect on turbinate deposition efficiency. Both plume angle and administration angle were found to be important factors in determining deposition efficiency. For administration angles of 40 degrees or 50 degrees , maximal turbinate deposition efficiency (30-50%) occurred with plume angles of 55-65 degrees , whereas a 30 degrees administration angle gave an approximately 75% deposition efficiency for similar plume angles. Deposition efficiencies of approximately 90% could be achieved with plume angles <30 degrees using 30 degrees administration angles. Both the plume angle and administration angle are critical factors in determining deposition efficiency, while many other spray parameters, including particle size, have relatively minor influences on deposition within the nasal cavity.

Mechanisms of Pharmaceutical Aerosol Deposition in the Respiratory Tract

“…Materials penetrating the nasal valve available for deposition in the turbinate region are desirable. Both gamma scintigraphic measurements in human volunteers and nasal airway replicas have been used to study the deposition pattern of nasal delivery (62)(63)(64)(65)(66)(67). These studies identify several key parameters including plume angle, droplet size, plume velocity, and inspiratory flow rate that may influence the deposition pattern of nasal spray devices.…”

Effects of Localized Hydrophilic Mannitol and Hydrophobic Nelfinavir Administration Targeted to Olfactory Epithelium on Brain Distribution

“…The olfactory region is located in the upper back quartile of the nasal cavity in a narrow slit approximately 1-2 mm wide. Traditional nasal pump devices used in most nasal drug delivery studies in humans are estimated to only deposit ≤5% of a typical dose in the olfactory region (15). Typical nasal pumps tend to have a wide plume angle that mainly deposit on the respiratory epithelium which would lead primarily to uptake in the blood stream and limit the percentage of drug directly distributed to the brain.…”

A Comparison of the Deposition Patterns of Different Nasal Spray Formulations Using a Nasal Cast

“…Cheng et al (2001) found that larger droplets and a wider spray angle increased deposition in the anterior region. Similarly, Foo et al (2007) found that sprays with small plume angles deposited more posteriorly but with minimal dependence on droplet size or viscosity. However, not all literature reports are consistent with this theory.…”

“…The nose model was secured upright on a stand and connected to an Respirator Pump Model 613 (Harvard Apparatus, Holliston, MA, USA), which simulated a 15-breaths/min breathing pattern with a ratio of inspiration to expiration of 40/60 and a cycle volume of 700 mL/stroke. The administration angle has been shown to have a significant effect on the deposition pattern (Foo et al 2007;Kundoor and Dalby 2011;Shah et al 2013). The nasal spray was manually actuated at a 45 angle to the horizontal and at a nostril insertion depth of 5 mm into the cast upon inhalation.…”