Validity ofIn VitroTests on Aqueous Spray Pumps as Surrogates for Nasal Deposition, Absorption, and Biologic Response

Abstract

This research investigated the impact of the full range of in vitro spray characterization tests described in the FDA Draft Bioequivalence Guidance on nasal deposition pattern, pharmacokinetics, and biological response to nicotine administered by two aqueous nasal spray pumps in human volunteers. Nicotine was selected as a model drug (even though it is not locally acting) based on its ability to alter cardiac function and available plasma assay. Significant differences in pump performance-including mean volume diameters, spray angle, spray width, and ovality ratios-were observed between the two pumps. There were no significant differences in deposition pattern, or pharmacokinetic or pharmacodynamic response to the nasally administered nicotine. Although there were statistical differences in the in vitro tests between the two pumps, these differences did not result in significant alterations in the site of droplet deposition within the nose, the rate and extent of nicotine absorption, or the physiologic response it induced. These results suggest that current measures of in vitro performance, particularly spray angle and spray pattern (ovality), may not be clinically relevant. Additional research is needed to define what spray pump characteristics are likely to produce differences in deposition pattern and drug response.

A Computational Study of Nasal Spray Deposition Pattern in Four Ethnic Groups

“…(52) The choice of 1 m/s spray velocity was determined based on an earlier report by Frank et al (8) that showed higher nasal spray penetration at 1 m/s compared to 3 m/s and 10 m/s.…”

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.…”

Characterization of Stability and Nasal Delivery Systems for Immunization with Nanoemulsion-Based Vaccines

“…The delivery performance of any aerosolized droplets introduced via the nasal cavity depends on many factors, such as the design of the pump, the physical properties of the formulation, and the position of administration. (21)(22)(23)(24)(25) In this present work, we have examined the effects of PBS versus sodium chloride (NaCl) diluents on stability and potency of NE-based vaccines when stored at room temperature (accelerated conditions). We have also evaluated the ability to deliver NE-based vaccines using standard nasal spray devices.…”