Development of a Novel Color Based Method for Assessing Deposition Patterns of Nasal Sprays and Nebulized Aerosols

Abstract

Aqueous nasal sprays are widely used to treat patients with local diseases such as allergic rhinitis. Several nasally administered corticosteroid products are nearing patent expiration and are candidates for generic copies, which is driving interest in how bioequivalence will be established - possibly using clinical and scintigraphic methods, but these methods each have specific limitations, as does the existing practice of measuring spray pattern and plume geometry which have proven difficult to correlate with nasal deposition. To overcome these limitations this thesis focused on designing a simple and inexpensive method that allows simulation of nasal anatomy and airflow, and is able to visualize and quantify deposition patterns of nasal sprays. Initially, we used the method to compare deposition patterns of different nasal sprays and different nasal drug delivery devices. Results showed that lower viscosity formulations provided greater coverage than the higher viscosity formulation and the nebulizer covered a greater surface area than the spray pump we evaluated. We also systematically investigated the effect of various formulation and patient related factors, and inspiratory flow rate on nasal deposition pattern and the results obtained showed that inspiratory flow rate did not have a significant effect whereas formulation and patient related factors had a significant effect on deposition pattern. Since bioequivalence of nasal sprays is carried out using in vitro studies, we compared the method to laser based systems which are used to measure spray pattern and plume geometry and we found that both the methods yielded similar results. We also evaluated the use of the method on cascade impactor stages (to detect droplet deposition) and on model faces fitted with facemasks (to quantify unintended facial and ocular droplet deposition associated with nebulizer use). It revealed that impactor temperature does have an effect on the size of nebulized droplets and facemask design had a significant effect on unintended facial and ocular deposition of nebulized droplets. This thesis demonstrates that this approach can be used as an alternative tool to justifiably establish in vitro bioequivalence of nasally administered, locally acting drug solutions and also provide a scientific rationale for justifying patient instructions for use.