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Formulation Development of Fast Dissolving Microneedles Loaded with Cubosomes of Febuxostat: In Vitro and In Vivo Evaluation

Febuxostat is a widely prescribed drug for the treatment of gout, which is a highly prevalent disease worldwide and is a major cause of disability in mankind. Febuxostat suffers from several limitations such as gastrointestinal disturbances and low oral bioavailability. Thus, to improve patient comp...

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Autores principales: Patel, Brijesh, Thakkar, Hetal
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9863705/
https://www.ncbi.nlm.nih.gov/pubmed/36678853
http://dx.doi.org/10.3390/pharmaceutics15010224
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author Patel, Brijesh
Thakkar, Hetal
author_facet Patel, Brijesh
Thakkar, Hetal
author_sort Patel, Brijesh
collection PubMed
description Febuxostat is a widely prescribed drug for the treatment of gout, which is a highly prevalent disease worldwide and is a major cause of disability in mankind. Febuxostat suffers from several limitations such as gastrointestinal disturbances and low oral bioavailability. Thus, to improve patient compliance and bioavailability, transdermal drug delivery systems of Febuxostat were developed for obtaining enhanced permeation. Cubosomes of Febuxostat were prepared using a bottom-up approach and loaded into a microneedle using a micromolding technique to achieve better permeation through the skin. Optimization of the process and formulation parameters were achieved using our design of experiments. The optimized cubosomes of Febuxostat were characterized for various parameters such as % entrapment efficiency, vesicle size, Polydispersity index, Transmission electron microscopy, in vitro drug release, Small angle X-ray scattering, etc. After loading it in the microneedle it was characterized for dissolution time, axial fracture force, scanning electron microscopy, in vitro drug release, pore closure kinetics, etc. It was also evaluated for various ex vivo characterizations such as in vitro cell viability, ex vivo permeation, ex vivo fluorescence microscopy and histopathology which indicates its safety and better permeation. In vivo pharmacokinetic studies proved enhanced bioavailability compared with the marketed formulation. Pharmacodynamic study indicated its effectiveness in a disease-induced rat model. The developed formulations were then subjected to the stability study, which proved its stability.
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spelling pubmed-98637052023-01-22 Formulation Development of Fast Dissolving Microneedles Loaded with Cubosomes of Febuxostat: In Vitro and In Vivo Evaluation Patel, Brijesh Thakkar, Hetal Pharmaceutics Article Febuxostat is a widely prescribed drug for the treatment of gout, which is a highly prevalent disease worldwide and is a major cause of disability in mankind. Febuxostat suffers from several limitations such as gastrointestinal disturbances and low oral bioavailability. Thus, to improve patient compliance and bioavailability, transdermal drug delivery systems of Febuxostat were developed for obtaining enhanced permeation. Cubosomes of Febuxostat were prepared using a bottom-up approach and loaded into a microneedle using a micromolding technique to achieve better permeation through the skin. Optimization of the process and formulation parameters were achieved using our design of experiments. The optimized cubosomes of Febuxostat were characterized for various parameters such as % entrapment efficiency, vesicle size, Polydispersity index, Transmission electron microscopy, in vitro drug release, Small angle X-ray scattering, etc. After loading it in the microneedle it was characterized for dissolution time, axial fracture force, scanning electron microscopy, in vitro drug release, pore closure kinetics, etc. It was also evaluated for various ex vivo characterizations such as in vitro cell viability, ex vivo permeation, ex vivo fluorescence microscopy and histopathology which indicates its safety and better permeation. In vivo pharmacokinetic studies proved enhanced bioavailability compared with the marketed formulation. Pharmacodynamic study indicated its effectiveness in a disease-induced rat model. The developed formulations were then subjected to the stability study, which proved its stability. MDPI 2023-01-09 /pmc/articles/PMC9863705/ /pubmed/36678853 http://dx.doi.org/10.3390/pharmaceutics15010224 Text en © 2023 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
Patel, Brijesh
Thakkar, Hetal
Formulation Development of Fast Dissolving Microneedles Loaded with Cubosomes of Febuxostat: In Vitro and In Vivo Evaluation
title Formulation Development of Fast Dissolving Microneedles Loaded with Cubosomes of Febuxostat: In Vitro and In Vivo Evaluation
title_full Formulation Development of Fast Dissolving Microneedles Loaded with Cubosomes of Febuxostat: In Vitro and In Vivo Evaluation
title_fullStr Formulation Development of Fast Dissolving Microneedles Loaded with Cubosomes of Febuxostat: In Vitro and In Vivo Evaluation
title_full_unstemmed Formulation Development of Fast Dissolving Microneedles Loaded with Cubosomes of Febuxostat: In Vitro and In Vivo Evaluation
title_short Formulation Development of Fast Dissolving Microneedles Loaded with Cubosomes of Febuxostat: In Vitro and In Vivo Evaluation
title_sort formulation development of fast dissolving microneedles loaded with cubosomes of febuxostat: in vitro and in vivo evaluation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9863705/
https://www.ncbi.nlm.nih.gov/pubmed/36678853
http://dx.doi.org/10.3390/pharmaceutics15010224
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