Evaluation of in vitro Penetration of Fluticasone Propionate from MP-AzeFlu and Fluticasone Propionate Nasal Spray Through EpiAirway™606 Tissues Using Vertical Diffusion Cells

William E Berger,1 Claus Bachert,2 Robert Allara,3 Arkady Koltun,4 Ferdinand Kopietz,5 Joachim G Maus,5 Alexander D D’Addio3 1Allergy and Asthma Associates of Southern California, Mission Viejo, CA, USA; 2Ghent University Hospital, Ghent, Belgium; 3Meda Pharmaceuticals, Somerset, NJ, USA; 4Mylan Inc., Canonsburg, PA, USA; 5Meda Pharma GmbH & Co. KG (a Mylan Company), Bad Homburg, GermanyCorrespondence: William E BergerAllergy and Asthma Associates of Southern California, 27800 Medical Center Road #244, Mission Viejo, CA, USATel + 949-364-2900Fax + 949-365-0117Email weberger@uci.eduPurpose: Most patients with allergic rhinitis (AR) have moderate-to-severe disease, requiring complete and prompt relief when symptoms occur. The time course of fluticasone propionate (FP) penetration into nasal tissues after intranasal administration is not well characterized. The goal of this proof-of-concept study was to evaluate the mucosal penetration of FP from fixed-combination FP-azelastine nasal spray (MP-AzeFlu) compared with an FP-only nasal spray in an in vitro, 3-dimensional human bronchial tissue model.Materials and Methods: Absorption of FP from MP-AzeFlu and FP nasal spray was modeled using EpiAirway™ 606 (MatTek Corporation; Ashland, MA, USA) tissue cultured in vertical diffusion cells. The dosing amount of MP-AzeFlu was optimized in a pilot study. Based on the results of the pilot study, 10 μL of MP-AzeFlu (3.65 μg; n = 8) and 10 μL of FP nasal spray (5.00 μg; n = 8) were evaluated for penetration of tissue. Tissue integrity was monitored with Lucifer yellow. FP in the receiving media was quantified for each sample using liquid chromatography with tandem mass spectrometry.Results: MP-AzeFlu and FP nasal spray were associated with similar FP accumulation profiles in the receiving media, but the permeability of FP was greater for MP-AzeFlu during hours 0 to 6, suggesting faster absorption for MP-AzeFlu. No indications of compromised tissue integrity were found in any of the tested cells.Conclusion: The higher and more rapid penetration of FP from MP-AzeFlu supports the use of MP-AzeFlu for patients with AR, particularly when prioritizing fast and pronounced symptom relief.Keywords: absorption, allergic rhinitis, azelastine hydrochloride, mucosal penetration, pharmacology