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
Monday, March 5, 2018
South Hall A2 (Convention Center)
William E. Berger, MD MBA FAAAAI, Alex D'Addio, PhD, Robert Allara, Bindu Upadhyay, Arkady Koltun, MD, PhD, Ferdinand Kopietz, PhD, Joachim Maus, MD
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.