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, sulfobutylether-beta-cyclodextrin (SBECD) that results in significant solubility enhancement.

Highlights

Sulfobutylether-beta cyclodextrin-enabled remdesivir formulation is a molecularly disperse, amorphous, instantly soluble system.

The host-guest type interaction is based on the co-existence of inclusion phenomenon and electrostatic interactions as proved by NMR.

Solubilization power of SBECD for REM is both SBECD concentration- and pH-dependent.

The REM-SBECD composition has high excess of SBECD over remdesivir: 3 % REM over 97 % SBECD by weight.

Reconstitution properties of electrospun nanofiber form of the REM-SBECD complex surpass that of the freeze-dried forms.

Therapeutic use of antiviral REM (Verklury ™) was made possible by complexation of the drug with SBECD.

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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Article information: Lajos Szente, István Puskás, Tamás Sohajda, Erzsébet Varga, Panna Vass, Zsombor Kristóf Nagy, Attila Farkas, Bianka Várnai, Szabolcs Béni, Eszter Hazai. Carbohydrate Polymers, Volume 264, 2021. https://doi.org/10.1016/j.carbpol.2021.118011.