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

Autori
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

Izvornik
International journal of pharmaceutics (0378-5173) 624 (2022); 122038, 15

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
spray-drying ; ultrasonic nozzle ; nose-to-brain powder delivery ; donepezil ; olfactory deposition

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

POVEZANOST RADA