Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil

Pharmaceutics

MaríaJosé Rodríguez-Lagunas¹  María-Alexandra Cañas¹  AnaCristina Calpena²  LupeCarolina Espinoza²  Marcelle Silva-Abreu²  Lyda Halbaut²  Beatriz Clares³ 

[1] Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain;Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain;Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain;

关键词: Donepezil;    Alzheimer’s disease;    nanoemulsion;    mucoadhesion;    nose-to-brain;    Pluronic F-127;   

DOI  :  10.3390/pharmaceutics11020064

来源: DOAJ

【 摘 要 】

Donepezil (DPZ) is widely used in the treatment of Alzheimer’s disease in tablet form for oral administration. The pharmacological efficacy of this drug can be enhanced by the use of intranasal administration because this route makes bypassing the blood⁻brain barrier (BBB) possible. The aim of this study was to develop a nanoemulsion (NE) as well as a nanoemulsion with a combination of bioadhesion and penetration enhancing properties (PNE) in order to facilitate the transport of DPZ from nose-to-brain. Composition of NE was established using three pseudo-ternary diagrams and PNE was developed by incorporating Pluronic F-127 to the aqueous phase. Parameters such as physical properties, stability, in vitro release profile, and ex vivo permeation were determined for both formulations. The tolerability was evaluated by in vitro and in vivo models. DPZ-NE and DPZ-PNE were transparent, monophasic, homogeneous, and physically stable with droplets of nanometric size and spherical shape. DPZ-NE showed Newtonian behavior whereas a shear thinning (pseudoplastic) behavior was observed for DPZ-PNE. The release profile of both formulations followed a hyperbolic kinetic. The permeation and prediction parameters were significantly higher for DPZ-PNE, suggesting the use of polymers to be an effective strategy to improve the bioadhesion and penetration of the drug through nasal mucosa, which consequently increase its bioavailability.

【 授权许可】

Unknown