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Formulation, characterization, optimization, and in-vivo performance of febuxostat self-nano-emulsifying system loaded sublingual films

Febuxostat (FXS) is a potent antigout drug with poor water solubility and relative high first-pass effect leading to moderate oral bioavailability (<49%). This study aimed to increase FXS solubility and bioavailability by optimizing sublingual fast-dissolving films (SFs) containing a selected FXS...

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Autores principales: Habib, Basant A., Abd El-Samiae, Amina S., El-Houssieny, Boushra M., Tag, Randa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260042/
https://www.ncbi.nlm.nih.gov/pubmed/34176376
http://dx.doi.org/10.1080/10717544.2021.1927247
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author Habib, Basant A.
Abd El-Samiae, Amina S.
El-Houssieny, Boushra M.
Tag, Randa
author_facet Habib, Basant A.
Abd El-Samiae, Amina S.
El-Houssieny, Boushra M.
Tag, Randa
author_sort Habib, Basant A.
collection PubMed
description Febuxostat (FXS) is a potent antigout drug with poor water solubility and relative high first-pass effect leading to moderate oral bioavailability (<49%). This study aimed to increase FXS solubility and bioavailability by optimizing sublingual fast-dissolving films (SFs) containing a selected FXS self-nano-emulsifying system (s-SNES) previously prepared by our team. The s-SNES was loaded into SFs by solvent casting technique. A full factorial design (3(2)) was applied to study the effects of polymer and plasticizer types on mechanical characteristics and the dissolution profile of FXS from the SFs. Numerical optimization was performed to select the SF having highest desirability according to predetermined characteristics. The optimized SF (O-SF) contained 1 g of s-SNES, polyvinylpyrrolidone K30 (6%w/v), polyethylene glycol 300 (20%w/w of polymer wt.), and Avicel PH101 (0.5%w/v). O-SF showed good permeation of FXS through sheep sublingual tissue. Storage of O-SF for three months showed no significant change in the FXS dissolution profile. In-vivo performance of O-SF in rabbits was compared to that of oral marketed tablets (Staturic(®) 80 mg). A cross-over design was applied and pharmacokinetic parameters were calculated after ensuring absence of sequence effect. Statistical analysis revealed better performance for O-SF with significantly higher C(max), AUC(0–24), AUC(0–∞), apparent t(1/2) together with lower t(max), and apparent k(el) than marketed tablets. Relative bioavailability of O-SF compared to the marketed tablet was found to be 240.6%. This confirms the achievement of the study aims of improving dissolution rate and bioavailability of FXS using a patient-wise convenient formula.
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spelling pubmed-82600422021-07-13 Formulation, characterization, optimization, and in-vivo performance of febuxostat self-nano-emulsifying system loaded sublingual films Habib, Basant A. Abd El-Samiae, Amina S. El-Houssieny, Boushra M. Tag, Randa Drug Deliv Research Article Febuxostat (FXS) is a potent antigout drug with poor water solubility and relative high first-pass effect leading to moderate oral bioavailability (<49%). This study aimed to increase FXS solubility and bioavailability by optimizing sublingual fast-dissolving films (SFs) containing a selected FXS self-nano-emulsifying system (s-SNES) previously prepared by our team. The s-SNES was loaded into SFs by solvent casting technique. A full factorial design (3(2)) was applied to study the effects of polymer and plasticizer types on mechanical characteristics and the dissolution profile of FXS from the SFs. Numerical optimization was performed to select the SF having highest desirability according to predetermined characteristics. The optimized SF (O-SF) contained 1 g of s-SNES, polyvinylpyrrolidone K30 (6%w/v), polyethylene glycol 300 (20%w/w of polymer wt.), and Avicel PH101 (0.5%w/v). O-SF showed good permeation of FXS through sheep sublingual tissue. Storage of O-SF for three months showed no significant change in the FXS dissolution profile. In-vivo performance of O-SF in rabbits was compared to that of oral marketed tablets (Staturic(®) 80 mg). A cross-over design was applied and pharmacokinetic parameters were calculated after ensuring absence of sequence effect. Statistical analysis revealed better performance for O-SF with significantly higher C(max), AUC(0–24), AUC(0–∞), apparent t(1/2) together with lower t(max), and apparent k(el) than marketed tablets. Relative bioavailability of O-SF compared to the marketed tablet was found to be 240.6%. This confirms the achievement of the study aims of improving dissolution rate and bioavailability of FXS using a patient-wise convenient formula. Taylor & Francis 2021-06-26 /pmc/articles/PMC8260042/ /pubmed/34176376 http://dx.doi.org/10.1080/10717544.2021.1927247 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Habib, Basant A.
Abd El-Samiae, Amina S.
El-Houssieny, Boushra M.
Tag, Randa
Formulation, characterization, optimization, and in-vivo performance of febuxostat self-nano-emulsifying system loaded sublingual films
title Formulation, characterization, optimization, and in-vivo performance of febuxostat self-nano-emulsifying system loaded sublingual films
title_full Formulation, characterization, optimization, and in-vivo performance of febuxostat self-nano-emulsifying system loaded sublingual films
title_fullStr Formulation, characterization, optimization, and in-vivo performance of febuxostat self-nano-emulsifying system loaded sublingual films
title_full_unstemmed Formulation, characterization, optimization, and in-vivo performance of febuxostat self-nano-emulsifying system loaded sublingual films
title_short Formulation, characterization, optimization, and in-vivo performance of febuxostat self-nano-emulsifying system loaded sublingual films
title_sort formulation, characterization, optimization, and in-vivo performance of febuxostat self-nano-emulsifying system loaded sublingual films
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260042/
https://www.ncbi.nlm.nih.gov/pubmed/34176376
http://dx.doi.org/10.1080/10717544.2021.1927247
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