PhD Scientific Days 2022

Pharmaceutical Sciences II. (Poster discussion will take place in the Aula during the Coffee Break)

Molecular interactions in remdesivir-cyclodextrin systems probed by NMR and CE

Előadó neve

Várnai, Bianka

Előadó munkahelye

Department of Pharmacognosy, Semmelweis University

Előadó telefonszáma

+36304900040

Előadó e-mail címe

bnkvarnai@gmail.com

Az előadás címe

Molecular interactions in remdesivir-cyclodextrin systems probed by NMR and CE

Szerző(k) neve és munkahelye

Bianka Várnai1, Dóra Ujj2, Erzsébet Varga2, Tamás Sohajda3, Szabolcs Béni1
1 Department of Pharmacognosy, Semmelweis University, Budapest, Hungary
2 CycloLab, Cyclodextrin R&D Ltd, Budapest, Hungary
3 CarboHyde Zrt., Budapest, Hungary

Bemutatás módja

Poszter

Szekció

Pharmaceutical Sciences II. (Poster discussion will take place in the Aula during the Coffee Break)

Language of the presentation

Hungarian

Preferred session

Pharmaceutical Sciences

Összefoglaló szövege

Introduction
Remdesivir (REM), the first antiviral drug (Veklury™) approved by the FDA for the therapy of COVID-19 possesses low aqueous solubility, thus the final formulation necessitates a solubilizing excipient. For this purpose, the randomly substituted sulfobutylether-β-cyclodextrin (SBEβCD) is used.
Aims
In this study we aimed at determining the intermolecular interactions between REM and various β- and γ-cyclodextrin (CD) derivatives by NMR spectroscopy to understand their interactions at the atomic level. Moreover, as the synthesis of REM provides a diastereomeric mixture of RP- and SP-REM bearing different pharmacological properties, we also aimed to explore the selectivity of various CDs towards REM diastereomers by capillary electrophoresis (CE).
Results
1H NMR titrations were performed to determine the stability constants of various CDs and REM at pH 2.0. Job’s method was used to determine the stoichiometries and it resulted in a 1:1 complex in each case. The NMR data revealed that the anionic sulfobutylether-sidechains of the hosts contribute to a significant stability enhancement (γCD < SBEγCD < βCD < SBEβCD < per-6-SBEβCD), and the primary side sulfobutylation of the host plays a critical role in this process. The complex structures were proposed based on the 2D ROESY NMR data. The applicability of CD derivatives to separate RP- and SP-REM in CE (using a pH 9.0 background electrolyte containing up to 20 mM selector) was also investigated. It was found that sugammadex (SGM) provides the highest resolution (Rs = 5.9 at 20 mM SGM) of REM diastereomers and their separation is driven by stability differences. The separation mechanism in CE has also been supported by NMR results investigating the individual REM isomers with SGM.
Funding
Supported by the New National Excellence Program of the Ministry of Innovation and Technology (ÚNKP-21-3-I-SE-52).

University and Doctoral School

Semmelweis University, Doctoral School of Pharmaceutical Sciences

Supervisor

Szabolcs Béni

Publication of my abstract

I give consent to the publication of my abstract on the website of the congress.

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

5980

Start

10:45

End

10:50

Authors (legacy)

Bianka Várnai1, Dóra Ujj2, Erzsébet Varga2, Tamás Sohajda3, Szabolcs Béni1
1 Department of Pharmacognosy, Semmelweis University, Budapest, Hungary
2 CycloLab, Cyclodextrin R&D Ltd, Budapest, Hungary
3 CarboHyde Zrt., Budapest, Hungary