Tailoring functional spray-dried powder platform for efficient donepezil nose-to-brain delivery

[Display omitted] Shortcomings of oral donepezil administration in the treatment of Alzheimer’s disease have paved the way for ongoing investigations towards more efficient and safe donepezil nose-to-brain delivery. Herein we present the development of advantageous powder platform for donepezil nose...

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Veröffentlicht in:International journal of pharmaceutics 2022-08, Vol.624, p.122038-122038, Article 122038
Hauptverfasser: Perkušić, Mirna, Nižić Nodilo, Laura, Ugrina, Ivo, Špoljarić, Drago, Jakobušić Brala, Cvijeta, Pepić, Ivan, Lovrić, Jasmina, Matijašić, Gordana, Gretić, Matija, Zadravec, Dijana, Kalogjera, Livije, Hafner, Anita
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Sprache:eng
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Zusammenfassung:[Display omitted] Shortcomings of oral donepezil administration in the treatment of Alzheimer’s disease have paved the way for ongoing investigations towards more efficient and safe donepezil nose-to-brain delivery. Herein we present the development of advantageous powder platform for donepezil nose-to-brain delivery, coupling careful design of chitosan and mannitol-based carrier matrix with spray-drying technology advantages and early consideration of adequate nasal administration mode, employing QbD approach. Unprecedentedly, ultrasonic nozzle was used to atomise the drying feed in response to size-related requirements for nasal aerosol particles. The optimised spray-drying process resulted in free-flowable dry powder with a great majority of particles larger than 10 µm, ensuring localised nasal deposition upon aerosolization, as evidenced by using 3D-printed nasal cavity model. QbD approach coupling formulation, process and administration parameters enabled optimisation of drug deposition profile reaching tremendously high 65.5 % of the applied dose deposited in the olfactory region. The leading formulation exhibited favourable swelling, mucoadhesion, drug release and permeation-enhancing properties, suiting the needs for efficient brain-targeted delivery. Results of in vitro biocompatibility and physico-chemical stability studies confirmed the leading formulation potential for safe and efficient donepezil nose-to-brain delivery. The obtained results encourage extending the study to an appropriate in vivo model needed for the final proof-of-concept.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2022.122038