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Sulfobutylether-beta-cyclodextrin-enabled antiviral remdesivir: Characterization of electrospun- and lyophilized formulations

Veklury™ by Gilead Sciences, Inc., containing antiviral drug, remdesivir (REM) has received emergency authorization in the USA and in Europe for COVID-19 therapy. Here, for the first time, we describe details of the non-covalent, host-guest type interaction between REM and the solubilizing excipient...

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Autores principales: Szente, Lajos, Puskás, István, Sohajda, Tamás, Varga, Erzsébet, Vass, Panna, Nagy, Zsombor Kristóf, Farkas, Attila, Várnai, Bianka, Béni, Szabolcs, Hazai, Eszter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025548/
https://www.ncbi.nlm.nih.gov/pubmed/33910715
http://dx.doi.org/10.1016/j.carbpol.2021.118011
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author Szente, Lajos
Puskás, István
Sohajda, Tamás
Varga, Erzsébet
Vass, Panna
Nagy, Zsombor Kristóf
Farkas, Attila
Várnai, Bianka
Béni, Szabolcs
Hazai, Eszter
author_facet Szente, Lajos
Puskás, István
Sohajda, Tamás
Varga, Erzsébet
Vass, Panna
Nagy, Zsombor Kristóf
Farkas, Attila
Várnai, Bianka
Béni, Szabolcs
Hazai, Eszter
author_sort Szente, Lajos
collection PubMed
description Veklury™ by Gilead Sciences, Inc., containing antiviral drug, remdesivir (REM) has received emergency authorization in the USA and in Europe for COVID-19 therapy. Here, for the first time, we describe details of the non-covalent, host-guest type interaction between REM and the solubilizing excipient, sulfobutylether-beta-cyclodextrin (SBECD) that results in significant solubility enhancement. Complete amorphousness of the cyclodextrin-enabled REM formulation was demonstrated by X-ray diffraction, thermal analysis, Raman chemical mapping and electron microscopy/energy dispersive spectroscopy. The use of solubilizing carbohydrate resulted in a 300-fold improvement of the aqueous solubility of REM, and enhanced dissolution rate of the drug enabling the preparation of stable infusion solutions for therapy. 2D ROESY NMR spectroscopy provided information on the nature of REM–excipient interaction and indicated the presence of inclusion phenomenon and the electrostatic attraction between anionic SBECD and nitrogen-containing REM in aqueous solution.
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spelling pubmed-80255482021-04-07 Sulfobutylether-beta-cyclodextrin-enabled antiviral remdesivir: Characterization of electrospun- and lyophilized formulations Szente, Lajos Puskás, István Sohajda, Tamás Varga, Erzsébet Vass, Panna Nagy, Zsombor Kristóf Farkas, Attila Várnai, Bianka Béni, Szabolcs Hazai, Eszter Carbohydr Polym Article Veklury™ by Gilead Sciences, Inc., containing antiviral drug, remdesivir (REM) has received emergency authorization in the USA and in Europe for COVID-19 therapy. Here, for the first time, we describe details of the non-covalent, host-guest type interaction between REM and the solubilizing excipient, sulfobutylether-beta-cyclodextrin (SBECD) that results in significant solubility enhancement. Complete amorphousness of the cyclodextrin-enabled REM formulation was demonstrated by X-ray diffraction, thermal analysis, Raman chemical mapping and electron microscopy/energy dispersive spectroscopy. The use of solubilizing carbohydrate resulted in a 300-fold improvement of the aqueous solubility of REM, and enhanced dissolution rate of the drug enabling the preparation of stable infusion solutions for therapy. 2D ROESY NMR spectroscopy provided information on the nature of REM–excipient interaction and indicated the presence of inclusion phenomenon and the electrostatic attraction between anionic SBECD and nitrogen-containing REM in aqueous solution. Elsevier Ltd. 2021-07-15 2021-04-07 /pmc/articles/PMC8025548/ /pubmed/33910715 http://dx.doi.org/10.1016/j.carbpol.2021.118011 Text en © 2021 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Szente, Lajos
Puskás, István
Sohajda, Tamás
Varga, Erzsébet
Vass, Panna
Nagy, Zsombor Kristóf
Farkas, Attila
Várnai, Bianka
Béni, Szabolcs
Hazai, Eszter
Sulfobutylether-beta-cyclodextrin-enabled antiviral remdesivir: Characterization of electrospun- and lyophilized formulations
title Sulfobutylether-beta-cyclodextrin-enabled antiviral remdesivir: Characterization of electrospun- and lyophilized formulations
title_full Sulfobutylether-beta-cyclodextrin-enabled antiviral remdesivir: Characterization of electrospun- and lyophilized formulations
title_fullStr Sulfobutylether-beta-cyclodextrin-enabled antiviral remdesivir: Characterization of electrospun- and lyophilized formulations
title_full_unstemmed Sulfobutylether-beta-cyclodextrin-enabled antiviral remdesivir: Characterization of electrospun- and lyophilized formulations
title_short Sulfobutylether-beta-cyclodextrin-enabled antiviral remdesivir: Characterization of electrospun- and lyophilized formulations
title_sort sulfobutylether-beta-cyclodextrin-enabled antiviral remdesivir: characterization of electrospun- and lyophilized formulations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025548/
https://www.ncbi.nlm.nih.gov/pubmed/33910715
http://dx.doi.org/10.1016/j.carbpol.2021.118011
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