Naslov
Development of powder nasal forms for donepezil hydrochloride: assessment of nasal discomfort by mucosal irritation assay

Autori
Perkušić, Mirna ; Nižić Nodilo, Laura ; Matijašić, Gordana ; Trenkel, Marie ; Kühnl, Cord ; Scherließ, Regina ; Hafner, Anita

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, znanstveni

Skup
7th International Conference on Pharmaceutics and Advanced Drug Delivery Systems

Mjesto i datum
London, Ujedinjeno Kraljevstvo, 27.03.2023. - 28.03.2023

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Nasal delivery ; Donepezil ; Spray-drying ; Powder blending ; Lactose ; Mannitol ; Sensory effects

Sažetak
Nasal delivery of the anti-dementia drug donepezil hydrochloride (DH) presents an alternative route of administration directly to the brain. Nasal powders stand out as formulations with great potential for nose-to-brain delivery. However, due to close contact of powders and the mucosa, formulations can cause stinging, itching and/or burning (SIB) sensations. The slug mucosal irritation assay is a quick and accurate screening method for early prediction of nasal discomfort caused by powders. DH-loaded chitosan, chitosan/mannitol and chitosan/lactose microspheres were prepared by spray-drying (Büchi Mini Spray Dryer B-290, equipped with ultrasonic nozzle). Furthermore, DH-loaded chitosan microspheres were blended (Turbula® shaker mixer) with sieved (45-63 µm) or spray-dried mannitol and lactose, reaching the same constituent weight ratios as in spray-dried hybrid microspheres. The particle size distribution and morphology were determined by laser diffraction method (Malvern Mastersizer 3000) and scanning electron microscopy (Tescan Vega 3), respectively. The slug mucosal irritation assay was performed to screen the powders regarding their potential to cause SIB sensations. DH-loaded nasal powders were successfully prepared by spray-drying and/or powder blending. All spray-dried particles (Dv50 9.7±0.0-29.0±1.2 µm) were smaller than sieved lactose and mannitol. The tested nasal powders showed either no discomfort or mild discomfort. Statistically significant increase in irritability compared to negative control was observed only for DH-loaded chitosan microspheres and their mixture with sieved lactose. The obtained results indicate the superior sensory effects of hybrid microspheres compared to chitosan microspheres and reveal the possible combined impact of filler particle size and morphology on the powder blend irritability. Slug mucosal irritation assay proved to be a useful tool for evaluation of nasal discomfort early in the formulation development. Prepared DH powders generally showed low irritability, confirming the appropriate selection of excipients and suitability of the spray-drying process to adjust particle morphology.

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

Napomena
Poster je prezentiran online u sklopu virtualnog
seminara u okviru kongresa.

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