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Article

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

1
Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
2
Departamento de Química y Ciencias Exactas, Universidad Técnica Particular de Loja, Loja 1101608, Ecuador
3
Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain
4
Pharmacy and Pharmaceutical Technology Department, Faculty of Pharmacy, University of Granada, 18071 Granada, Spain
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Department of Biochemistry and Physiology, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain
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Institut de Recerca en Nutrició i Seguretat Alimentària (INSA), Universitat de Barcelona (UB), 08028 Barcelona, Spain
7
Biosanitary Institute of Granada (ibs.GRANADA), University Hospitals of Granada-University of Granada, 18012 Granada, Spain
*
Author to whom correspondence should be addressed.
Pharmaceutics 2019, 11(2), 64; https://doi.org/10.3390/pharmaceutics11020064
Received: 30 November 2018 / Revised: 21 January 2019 / Accepted: 29 January 2019 / Published: 1 February 2019
(This article belongs to the Special Issue Nose to Brain Delivery)
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. View Full-Text
Keywords: Donepezil; Alzheimer’s disease; nanoemulsion; mucoadhesion; nose-to-brain; Pluronic F-127 Donepezil; Alzheimer’s disease; nanoemulsion; mucoadhesion; nose-to-brain; Pluronic F-127
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MDPI and ACS Style

Espinoza, L.C.; Silva-Abreu, M.; Clares, B.; Rodríguez-Lagunas, M.J.; Halbaut, L.; Cañas, M.-A.; Calpena, A.C. Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil. Pharmaceutics 2019, 11, 64. https://doi.org/10.3390/pharmaceutics11020064

AMA Style

Espinoza LC, Silva-Abreu M, Clares B, Rodríguez-Lagunas MJ, Halbaut L, Cañas M-A, Calpena AC. Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil. Pharmaceutics. 2019; 11(2):64. https://doi.org/10.3390/pharmaceutics11020064

Chicago/Turabian Style

Espinoza, Lupe C., Marcelle Silva-Abreu, Beatriz Clares, María J. Rodríguez-Lagunas, Lyda Halbaut, María-Alexandra Cañas, and Ana C. Calpena 2019. "Formulation Strategies to Improve Nose-to-Brain Delivery of Donepezil" Pharmaceutics 11, no. 2: 64. https://doi.org/10.3390/pharmaceutics11020064

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