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

Abstract

Purpose

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

Acknowledgments

The abstract of this paper was presented at the AAAAI/WAO Joint Congress as a poster presentation in March 2018. The poster’s abstract was published in “Poster Abstracts” in The Journal of Allergy and Clinical Immunology: https://doi.org/10.1016/j.jaci.2017.12.957.

Abbreviations

AR, allergic rhinitis; FP, fluticasone propionate; LC-MS/MS, liquid chromatography with tandem mass spectrometry; PK, pharmacokinetic.

Author Contributions

All authors contributed to data analysis, drafting or revising the article, gave final approval of the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

WEB reports personal fees from AstraZeneca, ALK, Regeneron/Sanofi Genzyme, Optinose, Boehringer Ingelheim, and Kaleo, outside the submitted work. CB serves on the Speakers Bureau for Mylan Inc. RA was an employee of Meda Pharmaceuticals (now Mylan Inc.) at the time of the study. AK is an employee of Mylan Inc., USA. FK and JM are employees of Meda Pharma GmbH & Co. KG (a Mylan company), Germany. AD was an employee of Meda Pharmaceuticals (now Mylan Inc.) at the time of the study and is an independent consultant and president of Daddio Pharma Consulting LLC. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study was supported by Meda Pharma GmbH & Co. KG (a Mylan Company), Bad Homburg, Germany.