engleski

Formulation parameters in the development of powder platform for donepezil hydrochloride nasal delivery

INTRODUCTION Donepezil hydrochloride (DH) is widely used for the symptomatic treatment of Alzheimer’s disease (AD), currently available only in form for oral administration. Oral administration of DH presents low bioavailability in the brain, first-pass metabolism and unwanted gastrointestinal side effects [1]. Nasal delivery of DH proposes an alternative route of administration directly to central nervous system. Nasal powders have shown encouraging results in nose-to-brain drug delivery [2]. The purpose of this study is to set the basis in the development of powder delivery platform suitable for DH nasal delivery. MATERIALS AND METHODS DH nasal powders were prepared by spray drying using Büchi Mini Spray Dryer B-290, equipped with ultrasonic nozzle. Spray dried solutions contained DH, low molecular weight chitosan and/or mannitol or lactose monohydrate. Microspheres were characterized in terms of entrapment efficiency, particle size and zeta potential, flow properties and spray cone angle. Nasal deposition studies were performed using a representative 3D printed nasal cast connected to respiratory pump simulating breathing conditions. RESULTS DH nasal powders have been successfully prepared. Under formulation, process and administration parameters employed, appropriate window of particle size (greater than 10 µm), flow properties (Hausner ratio between 1.16 and 1.25) and spray cone angle (17.5-19.8º) was reached resulting in targeted deposition pattern within the nasal cavity. CONCLUSION Preliminary studies revealed the formulation parameters to be included in experimental design aiming to enlighten a relation of DH nasal powder properties to deposition pattern. Such an approach potentiates the development of DH nasal powder delivery platform with built-in qualities, maximizing cost and time saving. Acknowledgement This work has been supported in part by Croatian Science Foundation under the project UIP-2017-05-4592 and European Social Fund under the Croatian Science Foundation project DOK- 2020-01-2473. REFERENCES 1. Agrawal M, et al. J. Control. Release (2018) 281:139-177. 2. Giuliani A, et al. Drug Deliv. (2018) 25:376- 378.

nasal drug delivery ; spray-dried microspheres ; donepezil hydrochloride ; 3D printed nasal cast

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