Improved Olfactory Deposition of Theophylline Using a Nanotech Soft Mist Nozzle Chip

Madeline X. Zhang,Frank Verhoeven, Pieter Ravensbergen,Stefan Kooij, Rick Geoffrion,Daniel Bonn,Cees J. M. van Rijn

PHARMACEUTICS(2024)

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Abstract
Currently, nasal administration of active pharmaceutical ingredients is most commonly performed using swirl-nozzle-based pump devices or pressurized syringes. However, they lead to limited deposition in the more active regions of the nasal cavity, especially the olfactory region, which is crucial for nose-to-brain drug delivery. This research proposes to improve deposition in the olfactory region by replacing the swirl nozzle with a nanoengineered nozzle chip containing micrometer-sized holes, which generates smaller droplets of 10-50 mu m travelling at a lower plume velocity. Two nanotech nozzle chips with different hole sizes were tested at different inhalation flow rates to examine the deposition patterns of theophylline, a hyposmia treatment formulation, using a nasal cavity model. A user study was also conducted and showed that the patient instructions influenced the inhalation flow rate characteristics. Targeted flow rates of between 0 and 25 L/min were used for the in vitro deposition study, yielding 21.5-31.5% olfactory coverage. In contrast, the traditional swirl nozzle provided only 10.8% coverage at a similar flow rate. This work highlights the potential of the nanotech soft mist nozzle for improved intranasal drug delivery, particularly to the olfactory region.
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Key words
aerosol,nebulizer,olfactory region,intranasal delivery,soft mist,nanotechnology
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