Racemisation of (1R, 6S)- 8-benzyl-7,9-dioxo-2,8-diazabicyclo[4.3.0]nonane using Halogenated Solvent in Basic Medium

Bhavsar, Jigar; Bhashkar, Bhuwan; Kumar, Anil

doi:10.13005/ojc/290138

Cited by 2 publications

(1 citation statement)

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“…Till date, three anhydrous polymorphs (Forms I, II, and N), an amorphous and amorphous solid dispersion were reported for this drug substance . Besides, several solvate forms of VOX have also been reported . Among the three anhydrous forms reported for the VOX free base, Form-N was found to be the most stable compared to Forms I and II at room temperature.…”

Section: Introductionmentioning

confidence: 98%

Novel Pharmaceutical Cocrystal of Voxelotor, a Hemoglobin Oxygen Affinity Modulator: Synthesis, Crystal Structure, and Physicochemical Properties

Kammari,

Saladi,

Garai

et al. 2023

Crystal Growth & Design

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Voxelotor (VOX), a small-molecule BCS class-II drug, is used for the treatment of sickle cell disease. The USFDA granted accelerated approval for this drug molecule in 2019 as a first-in-class medication. A novel 1:0.5 cocrystal of voxelotor with a pharmaceutically acceptable coformer, oxalic acid (OA), has been identified to ameliorate the aqueous solubility of the drug and characterized using various solid-state techniques such as PXRD, DSC, TGA, and Fourier transform infrared spectroscopy. Further, single crystals were successfully generated for both the voxelotor-OA cocrystal (VOX-OA) and the VOX free base (Form-II) to have structural insights. Crystal structure analysis has been performed to understand the torsional/interplanar angles, hydrogen bonds, packing of the molecules, and other weak interactions for both the forms (cocrystal and Form-II) using single-crystal XRD studies. In addition, Hirshfeld surface analysis has been performed to delineate the intermolecular interactions quantitatively. The equilibrium solubility revealed that VOX-OA exhibited superior performances compared to VOX Form-II (marketed form) at pH conditions of 4.5 and 6.8. The hemi-OA cocrystal of voxelotor is stable enough under formulation stress conditions such as drying, milling, 10 ton pressure, open exposure, and humidity exposure. The cocrystal was found to be stable in the excipient compatibility study as no polymorphic transformation of the cocrystal is observed.

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Section: Introductionmentioning

confidence: 98%