Instillation of a Dry Powder in Nasal Casts: Parameters Influencing the Olfactory Deposition With Uni- and Bi-Directional Devices

Abstract

Nose-to-brain delivery is a promising way to reach the central nervous system with therapeutic drugs. However, the location of the olfactory region at the top of the nasal cavity complexifies this route of administration. In this study, we used a 3D-printed replica of a nasal cavity (a so-called “nasal cast”) to reproduce in vitro the deposition of a solid powder. We considered two different delivery devices: a unidirectional device generating a classical spray and a bidirectional device that relies on the user expiration. A new artificial mucus also coated the replica. Five parameters were varied to measure their influence on the powder deposition pattern in the olfactory region of the cast: the administration device, the instillation angle and side, the presence of a septum perforation, and the flow rate of possible concomitant inspiration. We found that the unidirectional powder device is more effective in targeting the olfactory zone than the bi-directional device. Also, aiming the spray nozzle directly at the olfactory area is more effective than targeting the center of the nasal valve. Moreover, the choice of the nostril and the presence of a perforation in the septum also significantly influence the olfactory deposition. On the contrary, the inspiratory flow has only a minor effect on the powder outcome. By selecting the more efficient administration device and parameters, 44% of the powder can reach the olfactory region of the nasal cast.

In vitro Evaluation of Paliperidone Palmitate Loaded Cubosomes Effective for Nasal-to-Brain Delivery

“…These values follow those previously observed using similar UDS and caffeine as a drug model (16.8° ± 2.4°). 47 A narrow plume angle seems to decrease the impaction in the nasal valve, increasing the postnasal-valve deposition. 84–86 For powder formulation, the plume angle is only affected by the administration device.…”

“…We used the 3D-printed nasal replica (called “nasal cast”) described by Rigaut et al to assess the deposition profile of our formulations. 47 The selected patient has normal anatomy without any anatomical disorder. The nasal cast is a new in vitro test to evaluate drug deposition in a nasal cavity.…”

“…Each part of the nasal cast was coated with an artificial mucus based on a thermosensitive gel (liquid under 10°C and swells around 18°C) composed of 25% w/w of Poloxamer ® 407 mixed into a simulated nasal electrolyte solution (SNES). 47 , 56 We introduced an exact amount of around 20 mg of powder into the device since the maximal dose for nasal delivery is 25 mg per nostril. 37 , 57 A previous study allowed us to determine the optimal parameters to target the olfactory zone.…”

“… 37 , 57 A previous study allowed us to determine the optimal parameters to target the olfactory zone. 47 The insertion angle was fixed with a direct aim of the olfactory zone (sagittal angle of 39° on the right and 29° on the left, and coronal angle of 20° on the right and 5° on the left, both pointing inwards). There was no concomitant inspiratory flow, and the powder was injected with a UDS device (Aptar Pharma, Le Vaudreuil, France).…”

“…As described below, to cover the whole process of N2B delivery, we also used a nasal cast as a new tool for nasal in vitro assessment to map the pharmaceutic forms in the nasal cavities. 47 …”