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The exhalation delivery system with fluticasone propionate (Xhance®) has been shown to deliver drug substantially more broadly in the nasal cavity (particularly into superior/posterior regions), with less off-target loss of drug to drip-out and swallowing, than conventional nasal sprays. This open-label study evaluated the systemic bioavailability of Xhance® by comparing the pharmacokinetic (PK) properties of a single dose of fluticasone from 3 products administering the drug using 3 different devices: Xhance®, Flonase® (fluticasone propionate inhalational nasal spray), and Flovent® HFA (fluticasone propionate inhalational aerosol). This open-label study was conducted in 2 parts. Study part 1 compared systemic exposure with a single dose of Xhance® 186 or 372 μg versus Flonase® 400 μg (3-way, 3-treatment, 3-sequence, randomized crossover in healthy subjects; n = 90). A separate study, part 2, under the same umbrella protocol, compared systemic exposure with Xhance® 372 μg versus Flovent® HFA 440 μg (2-way, 2-treatment, 2-sequence, randomized crossover in patients with mild to moderate asthma; n = 30). With Xhance® 186 μg, the geometric least squares mean (LSM) C max was higher than with Flonase® 400 μg (16.02 vs 11.66 pg/mL, respectively; geometric mean ratio [GMR], 137.42%) and the geometric LSM AUC 0–∞ values were similar (97.30 vs 99.61 pg · h/mL; GMR, 97.78%). With Xhance® 372 μg, the geometric LSM C max and AUC 0–∞ were higher than with Flonase® 400 μg (C max , 23.50 vs 11.66 pg/mL [GMR, 201.53%]; AUC 0–∞ , 146.61 vs 99.61 pg · h/mL [GMR, 147.19%]). In part 2, the geometric LSM C max and AUC 0–∞ values were lower with Xhance® 372 μg than with Flovent® HFA 440 μg (C max , 25.28 vs 40.02 pg/mL [GMR, 63.18%]; AUC 0–∞ , 205.78 vs 415.16 pg · h/mL [GMR, 49.57%]). Similar intranasal doses of Xhance® (372 μg) and Flonase® (400 μg) are clearly not bioequivalent. Systemic exposure is very low with all products. Systemic exposure is higher with Xhance® than with Flonase® and substantially lower than with Flovent® HFA 440 μg and, based on dose normalization, Flovent® HFA 220 μg. ClincalTrials.gov identifier: NCT02266927. [ABSTRACT FROM AUTHOR]

Computational fluid dynamics (CFD) has been used to investigate the intranasal deposition of corticosteroid sprays. CFD Lagrangian tracking models terminate particle motion once particles come into contact with a surface ("trap" boundary condition) and disregard the liquid film buildup on the mucosal surfaces of the sinonasal cavity walls. However, the interaction between spray droplets and the mucosal surface is critical for corticosteroid delivery using the exhalation delivery system (EDS) nasal spray device. Droplets coalesce on sinonasal walls, forming a thin "wall-film" on which droplets spread along the surface, splash, and/or break into secondary particles, depending on impact energy. To advance nasal drug delivery modeling, three CFD models of fluticasone propionate deposition using the EDS device in a Draf III post-surgical geometry were developed: (1) using traditional "trap" boundary conditions; (2) using "wall-film" boundary conditions and one-way coupling; and (3) using "wall-film" boundary conditions with two-way coupling (to account for the high-mass loading in the near-nozzle spray field). Contour plots and data sets for each CFD model were qualitatively compared with physical models in the same geometry (visualized in a 3D-printed sinonasal cast). The CFD simulations showed that EDS delivers fluticasone to all sinonasal regions, including areas superiorly and posteriorly in the sinonasal cavity. In addition, deposition improved and more closely correlated with physical experiments as the CFD model complexity evolved. "Wall-film" modeling of EDS delivery demonstrated increased surface coverage compared to the "trap" model. The "wall-film/two-way coupling" model demonstrated substantially higher deposition in the remote frontal and maxillary sinuses, agreeing with physical cast experiments. In conclusion, CFD simulation of EDS delivery using the "wall-film" boundary/two-way coupling model appears to most accurately represent observations from physical model experiments in the same geometry. • We created CFD models of drug deposition with the exhalation delivery system (EDS). • An iterative process improved CFD model simulation of deposition in nasal casts. • The most accurate CFD model used "Wall-film" conditions and two-way coupling. • CFD simulations and cast studies suggest EDS delivers drug to all sinonasal regions. [ABSTRACT FROM AUTHOR]