Naslov
Development of nasal donepezil powder platform employing statistical design

Autori
Perkušić, Mirna ; Nižić Nodilo, Laura ; Ugrina, Ivo ; Špoljarić, Drago ; Jakobušić Brala, Cvijeta ; Pepić, Ivan ; Zadravec, Dijana ; Kalogjera, Livije ; Hafner, Anita

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
FIGON & EUFEPS European Medicines Days 2022 Book of Abstracts / - , 2022, 60-60

Skup
FIGON & EUFEPS European Medicines Days 2022

Mjesto i datum
Liblice, Češka Republika, 01.06.2022. - 03.06.2022

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
nasal drug delivery ; spray-dried microparticles ; chitosan ; donepezil ; 3D printed nasal cast

Sažetak
Oral delivery of anti-dementia drug donepezil hydrochloride (DH) is related to several disadvantages such as gastrointestinal side effects and low bioavailability in the brain (1). Nasal administration of DH may provide its efficient and direct delivery to the brain via olfactory nerve that innervates olfactory region of the nasal cavity. Nasal powders have shown encouraging results in nose-to-brain drug delivery (2). This work aims to develop DH nasal powder platform by spray drying, employing Quality by Design (QbD) principles using statistical design of experiments (DoE). By coupling formulation, process and administration parameters the aim is to generate free-flowable powder with appropriate degree of swelling and spray cone angle, that will result in localised olfactory nasal deposition. DH nasal powders were prepared by spray dryer equipped with ultrasonic nozzle. Statistical design of experiments (JMP 14.0 software, USA) was employed in optimization of spray dried DH (Carbosynth Ltd., UK) loaded chitosan (Sigma Aldrich, USA) and mannitol (BDH Prolabo, UK) microspheres. DH loaded chitosan/mannitol (DH/C/M) were characterized in terms of flow properties, spray cone angle and degree of swelling. Nasal deposition studies were performed using a representative 3D printed nasal cast connected to respiratory pump simulating breathing conditions. Spray dried DH/C/M microspheres have been successfully prepared by spray drying. Powders exhibited adequate swelling: volume of simulated nasal fluid absorbed per mg of chitosan in the swelling process was between 27.7±2.8 and 67.0±0.7 mg/mL. Prepared microspheres were characterised in terms of flow properties (Hausner ratio between 1.15±0.06 and 1.32±0.07) and spray cone angle (22.5˚±0.5–28.3˚±0.9). QbD approach coupling formulation, process and administration parameters enabled optimisation of DH deposition profile reaching tremendously high percent of the applied dose deposited in the olfactory region (13.9±1.9– 65.5±0.2%). Statistical design enabled rational preparation of spray dried DH/C/M microspheres that showed favourable swelling and sprayability properties. Nasal deposition studies revealed the potential of strategy employed to deliver drug to the targeted regions of nasal cavity. References: 1. Agrawal M, et al. J. Control. Release. 2018. 281:139-177 2. Giuliani A, et al. Drug Deliv. 2018. 25:376-378

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

POVEZANOST RADA