engleski

Preparation of spray dried nasal donepezil powder platform using an ultrasonic nozzle

Nasal powders are promising platforms in nose-to- brain drug delivery (1). Spray drying is a single- step, fast and scalable dry powder preparation method (2). Design of experiments (DoE) is often used in product-related optimization of the spray drying process (2). The potential of ultrasonic nozzle for the preparation of nasal powders has not yet been deeply investigated. The aim of this study is to prepare donepezil loaded chitosan/mannitol microspheres by spray drying using an ultrasonic nozzle. Employing Quality by Design approach will enable elucidating and understanding the impact of formulation and process parameters on spray drying yield and microspheres physicochemical properties. Statistical DoE (JMP 14.0 software, USA) was employed in optimisation of spray dried donepezil hydrochloride (DH ; Carbosynth Ltd, UK) loaded chitosan (Sigma Aldrich, USA) and mannitol (BDH Prolabo, UK) microspheres. The following properties were observed as responses: process yield, entrapment efficiency (high performance liquid chromatography ; Perkin Elmer, USA), particle size (Mastersizer 3000 ; Malvern Instruments Ltd, UK) and moisture content (TA Instruments Q500 ; TA Instruments, USA). Microspheres morphology and surface properties were observed by scanning electron microscopy (SEM) using a Tescan Vega 3 microscope (Czech Republic). Spray dried chitosan/mannitol microspheres with high DH entrapment efficiency and adequate moisture content were successfully prepared using an ultrasonic nozzle, fitting the size requirements for targeted nasal delivery (majority of particles larger than 10 µm). Process yield was in line with literature reports. Regression modelling revealed the impact of both, formulation and process parameters on yield, moisture content and particle size. The obtained microspheres were uniform and spherical with smooth surface, as showed by SEM micrographs. This study confirmed the suitability of ultrasonic nozzle for preparation of microspheres for nasal drug delivery. Predictive power of regression model obtained for observed responses enables the development of donepezil loaded chitosan/mannitol nasal powder platform with built-in quality, maximizing cost and time savings. References: 1. Giuliani A, Balducci AG, Zironi E, Colombo G, Bortolotti F, Lorenzini L, Galligioni V, Pagliuca G, Scagliarini A, Calzà L, Sonvico F. Drug Deliv. 2018. 25:376-387 2. Ziaee A, Albadarin AB, Padrela L, Femmer T, O’Reilly E, Walker G. Spray drying of pharmaceuticals and biopharmaceuticals: Critical parameters and experimental process optimization approaches. Eur J Pharm Sci. 2019 ; 12: 300–318.

quality by design, spray drying, ultrasonic nozzle ; nasal drug delivery, donepezil

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