Evaluation of the in Vitro Penetration of Fluticasone Propionate (FP) from Azelastine Hydrochloride–Fluticasone Propionate Nasal Spray (MP-AzeFlu) & Fluticasone Propionate Nasal Spray through Epiairway™606 Tissues Using Vertical Diffusion Cells

Rationale: MP-AzeFlu has demonstrated superior efficacy vs FP in treating allergic rhinitis. In addition, pharmacokinetic studies have suggested that MP-AzeFlu may yield higher FP blood levels than a nasal spray containing FP alone. This study used normal human-derived tracheal/bronchial epithelial cells mounted in a vertical diffusion cell system to evaluate in vitro penetration of FP from MP-AzeFlu vs FP nasal spray into and across EpiAirway™606 tissues from aqueous suspension.

Methods: Donor solutions containing MP-AzeFlu (3.65 μg; n=8), FP nasal spray (5 μg; n=8), MP-AzeFlu placebo (n=1), and Lucifer yellow (280 μM; n=1) were applied to the ciliated apical surface (top) of EpiAirway™606 tissues equilibrated at 37°C. Aliquots from the receiver solution (bottom) of each sample were taken at 1, 2, 4, 6, 18, and 18.5 hrs to quantify FP via LC-MS/MS; Lucifer yellow (280 μM) was applied to each sample at 18 hrs to assess tissue integrity.

Results: FP penetrated through and into tissues in all cells dosed with MP-AzeFlu or FP nasal spray, with no indications of compromised tissue integrity. Both MP-AzeFlu and FP nasal spray demonstrated similar drug accumulation profiles for FP, indicating 2.5% drug delivery. After correcting for differences in FP concentration in each product, FP permeability was similar between treatments at 18 hrs but was significantly higher during 0–6 hrs with MP-AzeFlu compared with FP nasal spray (P=0.035).

Conclusions: While absolute amounts of FP were similar between treatments, FP permeation occurred more quickly with MP-AzeFlu than with FP nasal spray, suggesting earlier time to maximum FP plasma concentration with MP-AzeFlu.