Cargando…

Development and In Vitro-Ex Vivo Evaluation of Novel Polymeric Nasal Donepezil Films for Potential Use in Alzheimer’s Disease Using Experimental Design

The objective and novelty of the present study is the development and optimization of innovative nasal film of Donepezil hydrochloride (DH) for potential use in Alzheimer’s disease. Hydroxypropyl-methyl-cellulose E50 (factor A) nasal films, with Polyethylene glycol 400 as plasticizer (factor B), and...

Descripción completa

Detalles Bibliográficos
Autores principales: Papakyriakopoulou, Paraskevi, Rekkas, Dimitrios M., Colombo, Gaia, Valsami, Georgia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9416078/
https://www.ncbi.nlm.nih.gov/pubmed/36015368
http://dx.doi.org/10.3390/pharmaceutics14081742
_version_ 1784776390861651968
author Papakyriakopoulou, Paraskevi
Rekkas, Dimitrios M.
Colombo, Gaia
Valsami, Georgia
author_facet Papakyriakopoulou, Paraskevi
Rekkas, Dimitrios M.
Colombo, Gaia
Valsami, Georgia
author_sort Papakyriakopoulou, Paraskevi
collection PubMed
description The objective and novelty of the present study is the development and optimization of innovative nasal film of Donepezil hydrochloride (DH) for potential use in Alzheimer’s disease. Hydroxypropyl-methyl-cellulose E50 (factor A) nasal films, with Polyethylene glycol 400 as plasticizer (factor B), and Methyl-β-Cyclodextrin, as permeation enhancer (factor C), were prepared and characterized in vitro and ex vivo. An experimental design was used to determine the effects of the selected factors on permeation profile of DH through rabbit nasal mucosa (response 1), and on film flexibility/foldability (response 2). A face centered central composite design with three levels was applied and 17 experiments were performed in triplicate. The prepared films exhibited good uniformity of DH content (90.0 ± 1.6%–99.8 ± 4.9%) and thickness (19.6 ± 1.9–170.8 ± 11.5 μm), storage stability characteristics, and % residual humidity (<3%), as well as favourable swelling and mucoadhesive properties. Response surface methodology determined the optimum composition for flexible nasal film with maximized DH permeation. All selected factors interacted with each other and the effect of these interactions on responses is strongly related to the factor’s concentration ratios. Based on these encouraging results, in vivo serum and brain pharmacokinetic study of the optimized nasal film, in comparison to DH oral administration, is ongoing in an animal model.
format Online
Article
Text
id pubmed-9416078
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-94160782022-08-27 Development and In Vitro-Ex Vivo Evaluation of Novel Polymeric Nasal Donepezil Films for Potential Use in Alzheimer’s Disease Using Experimental Design Papakyriakopoulou, Paraskevi Rekkas, Dimitrios M. Colombo, Gaia Valsami, Georgia Pharmaceutics Article The objective and novelty of the present study is the development and optimization of innovative nasal film of Donepezil hydrochloride (DH) for potential use in Alzheimer’s disease. Hydroxypropyl-methyl-cellulose E50 (factor A) nasal films, with Polyethylene glycol 400 as plasticizer (factor B), and Methyl-β-Cyclodextrin, as permeation enhancer (factor C), were prepared and characterized in vitro and ex vivo. An experimental design was used to determine the effects of the selected factors on permeation profile of DH through rabbit nasal mucosa (response 1), and on film flexibility/foldability (response 2). A face centered central composite design with three levels was applied and 17 experiments were performed in triplicate. The prepared films exhibited good uniformity of DH content (90.0 ± 1.6%–99.8 ± 4.9%) and thickness (19.6 ± 1.9–170.8 ± 11.5 μm), storage stability characteristics, and % residual humidity (<3%), as well as favourable swelling and mucoadhesive properties. Response surface methodology determined the optimum composition for flexible nasal film with maximized DH permeation. All selected factors interacted with each other and the effect of these interactions on responses is strongly related to the factor’s concentration ratios. Based on these encouraging results, in vivo serum and brain pharmacokinetic study of the optimized nasal film, in comparison to DH oral administration, is ongoing in an animal model. MDPI 2022-08-21 /pmc/articles/PMC9416078/ /pubmed/36015368 http://dx.doi.org/10.3390/pharmaceutics14081742 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Papakyriakopoulou, Paraskevi
Rekkas, Dimitrios M.
Colombo, Gaia
Valsami, Georgia
Development and In Vitro-Ex Vivo Evaluation of Novel Polymeric Nasal Donepezil Films for Potential Use in Alzheimer’s Disease Using Experimental Design
title Development and In Vitro-Ex Vivo Evaluation of Novel Polymeric Nasal Donepezil Films for Potential Use in Alzheimer’s Disease Using Experimental Design
title_full Development and In Vitro-Ex Vivo Evaluation of Novel Polymeric Nasal Donepezil Films for Potential Use in Alzheimer’s Disease Using Experimental Design
title_fullStr Development and In Vitro-Ex Vivo Evaluation of Novel Polymeric Nasal Donepezil Films for Potential Use in Alzheimer’s Disease Using Experimental Design
title_full_unstemmed Development and In Vitro-Ex Vivo Evaluation of Novel Polymeric Nasal Donepezil Films for Potential Use in Alzheimer’s Disease Using Experimental Design
title_short Development and In Vitro-Ex Vivo Evaluation of Novel Polymeric Nasal Donepezil Films for Potential Use in Alzheimer’s Disease Using Experimental Design
title_sort development and in vitro-ex vivo evaluation of novel polymeric nasal donepezil films for potential use in alzheimer’s disease using experimental design
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9416078/
https://www.ncbi.nlm.nih.gov/pubmed/36015368
http://dx.doi.org/10.3390/pharmaceutics14081742
work_keys_str_mv AT papakyriakopoulouparaskevi developmentandinvitroexvivoevaluationofnovelpolymericnasaldonepezilfilmsforpotentialuseinalzheimersdiseaseusingexperimentaldesign
AT rekkasdimitriosm developmentandinvitroexvivoevaluationofnovelpolymericnasaldonepezilfilmsforpotentialuseinalzheimersdiseaseusingexperimentaldesign
AT colombogaia developmentandinvitroexvivoevaluationofnovelpolymericnasaldonepezilfilmsforpotentialuseinalzheimersdiseaseusingexperimentaldesign
AT valsamigeorgia developmentandinvitroexvivoevaluationofnovelpolymericnasaldonepezilfilmsforpotentialuseinalzheimersdiseaseusingexperimentaldesign