Sulfobutylether-beta-cyclodextrin-enabled antiviral remdesivir: Characterization of electrospun- and lyophilized formulations.
Adenosine Monophosphate
/ analogs & derivatives
Alanine
/ analogs & derivatives
Antiviral Agents
/ chemistry
Calorimetry, Differential Scanning
Excipients
/ chemistry
Freeze Drying
/ methods
Magnetic Resonance Spectroscopy
Microscopy, Electron, Scanning
Molecular Docking Simulation
Nanofibers
/ chemistry
Powders
Solubility
Spectrum Analysis, Raman
X-Ray Diffraction
beta-Cyclodextrins
/ chemistry
COVID-19 Drug Treatment
2D ROESY NMR
Differential scanning calorimetry
Electrostatic interaction
Inclusion
RAMAN-mapping
Remdesivir
Solubilization
Sulfobutylether-beta-cyclodextrin
X-ray diffraction
Journal
Carbohydrate polymers
ISSN: 1879-1344
Titre abrégé: Carbohydr Polym
Pays: England
ID NLM: 8307156
Informations de publication
Date de publication:
15 Jul 2021
15 Jul 2021
Historique:
received:
28
01
2021
revised:
22
03
2021
accepted:
28
03
2021
entrez:
29
4
2021
pubmed:
30
4
2021
medline:
11
5
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33910715
pii: S0144-8617(21)00398-2
doi: 10.1016/j.carbpol.2021.118011
pmc: PMC8025548
pii:
doi:
Substances chimiques
Antiviral Agents
0
Excipients
0
Powders
0
beta-Cyclodextrins
0
SBE4-beta-cyclodextrin
2PP9364507
remdesivir
3QKI37EEHE
Adenosine Monophosphate
415SHH325A
Alanine
OF5P57N2ZX
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
118011Informations de copyright
Copyright © 2021 Elsevier Ltd. All rights reserved.
Références
Travel Med Infect Dis. 2020 May - Jun;35:101647
pubmed: 32247927
J Med Chem. 2017 Mar 9;60(5):1648-1661
pubmed: 28124907
mBio. 2018 Mar 6;9(2):
pubmed: 29511076
J Biochem. 2001 Mar;129(3):423-8
pubmed: 11226882
Int J Pharm. 2020 Jun 15;583:119396
pubmed: 32376442
Adv Drug Deliv Rev. 1999 Mar 1;36(1):17-28
pubmed: 10837706
Steroids. 2003 Jan;68(1):43-53
pubmed: 12475722
Pharm Res. 1996 Feb;13(2):256-64
pubmed: 8932446
Lancet. 2020 May 16;395(10236):1569-1578
pubmed: 32423584
J Comput Chem. 2010 Jan 30;31(2):455-61
pubmed: 19499576
J Biol Chem. 2020 Apr 10;295(15):4773-4779
pubmed: 32094225
J Cheminform. 2009 Sep 11;1:15
pubmed: 20150996
J Pharm Pharmacol. 2010 Nov;62(11):1607-21
pubmed: 21039545
N Engl J Med. 2020 Jun 11;382(24):2327-2336
pubmed: 32275812
J Control Release. 2019 Mar 28;298:120-127
pubmed: 30779951