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

Author:

Zhang Madeline X.1ORCID,Verhoeven Frank2,Ravensbergen Pieter2,Kooij Stefan1,Geoffrion Rick3,Bonn Daniel1ORCID,van Rijn Cees J. M.1ORCID

Affiliation:

1. Van der Waals-Zeeman Institute, Institute of Physics, University of Amsterdam, 1098 XH Amsterdam, The Netherlands

2. Medspray B.V., 7521 PV Enschede, The Netherlands

3. Cyrano Therapeutics Inc., Delray Beach, FL 33445, USA

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 μm 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.

Funder

Dutch Research Council

Publisher

MDPI AG

Subject

Pharmaceutical Science

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