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Sprayable in situ gelling fluticasone suspensions: nasal deposition upon bi-direcional delivery in vitro

Background: Nasal corticosteroids are the first- line therapy for nasal inflammatory disorders, however, superior effect of systemic over local corticosteroids shows room for improvement of local corticosteroid delivery. In situ gelling system presents advantageous nasal delivery platform. It can be easily sprayed as liquid in the nasal cavity and prolong contact time with nasal mucosa due to rapid gelation. It could be expected that effective nasal deposition of such innovative formulation platform could significantly improve local therapeutic effect of corticosteroids. One of the latest approaches to improve corticosteroid deposition within the targeted nasal region refers to bi-directional nasal delivery (Djupesland et al., 2006, Fokkens and Reitsma, 2018). The aim of our study is to assess the nasal deposition pattern of sprayable in situ gelling fluticasone suspensions upon simulated bi-directional delivery. Methods: In situ gelling suspensions were prepared using fluticasone propionate (Carbosynth Ltd., UK), pectin CF 025 (Herbstreith&Fox, Germany), gellan gum (Phytagel, Sigma-Aldrich, USA), sodium hyaluronate (Contipro, Czech Republic), Tween 80 (Sigma-Aldrich, USA) and mannitol (BDH Prolabo, UK). The formulations were characterised in terms of rheological properties (Rheometer MCR 102, Anton Paar, Austria), spray cone angle (measured by a virtual protractor after spraying against a dark background) and sprayability/droplet size distribution (Malvern Spraytec, UK). For the determination of deposition pattern of in situ gelling systems, the inner surface of a nasal cavity model (Koken Co Ltd., Japan) was evenly covered with Sar-gel® (Arkema Inc., Sartomer Americas, USA), a water- indicating paste. To simulate exhalation in bi- directional delivery, the model was connected to respiratory pump (Harvard Apparatus, USA). The suspensions were administered by using Spray Pump 3K (Aeropump, Germany) under different angles against horizontal and vertical (i.e. nasal septum) plane. Results: All formulations showed suitable rheological properties. Under formulation and administration parameters employed, appropriate window of droplet size distribution and spray angle was reached. The concept of bi-directional nasal delivery was successfully employed resulting in targeted deposition pattern within the nasal cavity. Conclusions: This research confirmed bi- directional nasal delivery as a useful way to deliver in situ gelling fluticasone suspensions to the targeted area within the nasal cavity.

Fluticasone ; Pectin ; Gellan gum ; Sodium hyaluronate ; In situ gelling ; Nasal deposition, Bi-directional delivery

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