In Vitro Measurement Of Regional Nasal Drug Delivery With Flonase,(R) Flonase (R) Sensimist,(Tm) And Mad Nasal (Tm) In Anatomically Correct Nasal Airway Replicas Of Pediatric And Adult Human Subjects

Background: The majority of current nasal delivery devices, commercialized for children, are developed for adults. Differences in the dose reaching the target are expected due to significant differences between the pediatric and adult nasal airway geometries and their inhalation patterns. This study aims to compare the efficacy of most common nasal drug delivery devices in terms of regional delivery of suspension and solution formulations in pediatric and adult subjects. Methods: Anatomically correct nasal models of 2-, 5-, and 50-year old subjects were developed to evaluate regional nasal delivery of suspensions of fluticasone propionate and fluticasone furoate delivered with Flonase (R) and Flonase (R) Sensimist (TM), respectively, and the delivery of an aqueous solution of a model drug, administered with MAD Nasal (TM). Relevant inhalation patterns were considered for each nasal airway geometry. Controlled administration methods were used, and all contributing parameters, including particle size, velocity, and plume geometry, are reported. Results: Regional deposition patterns resulting from Flonase (R) Sensimist (TM) and Flonase (R) were not significantly different in each replica (\documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\usepackage{upgreek}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document}$$p > 0.05$$\end{document}), despite their different plume geometry and droplet size distributions. However, there was a significant difference in deposition of nasal sprays between the pediatric (2- and 5-year old) and adult models (\documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\usepackage{upgreek}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document}$$p < 0.05$$\end{document}), while no statistical differences were found between the two pediatric models (\documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\usepackage{upgreek}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document}$$p > 0.05$$\end{document}). The MAD atomizer resulted in different deposition patterns in all three subjects (\documentclass{aastex}\usepackage{amsbsy}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{bm}\usepackage{mathrsfs}\usepackage{pifont}\usepackage{stmaryrd}\usepackage{textcomp}\usepackage{portland, xspace}\usepackage{amsmath, amsxtra}\usepackage{upgreek}\pagestyle{empty}\DeclareMathSizes{10}{9}{7}{6}\begin{document}$$p < 0.05$$\end{document}). Conclusion: Nasal sprays are not adequate delivery devices for pediatric population, due to the narrower nasal passage and greater anterior deposition (similar to 60%). MAD atomizer resulted in significantly less anterior deposition (similar to 10%-15%) compared to the nasal pumps, but there was similar to 30% run off to the throat. An in vitro platform incorporating anatomically correct nasal geometries and inhalation patterns can guide the development of age-appropriate nasal drug delivery devices.