Bromhexine and its fumarate salt: Crystal structures, Hirshfeld surfaces and dissolution study

Ya-An Zhang; Cui-Min Yan; Bai-Wang Sun; Lin-Xuan Wang

doi:10.1016/j.molstruc.2021.130154

Bromhexine and its fumarate salt: Crystal structures, Hirshfeld surfaces and dissolution study

J Mol Struct. 2021 Jun 5:1233:130154. doi: 10.1016/j.molstruc.2021.130154. Epub 2021 Feb 24.

Authors

Ya-An Zhang¹, Cui-Min Yan², Bai-Wang Sun², Lin-Xuan Wang¹

Affiliations

¹ School of Pharmaceutical and Chemical Engineering, Chengxian College, Southeast University, Nanjing 210088, PR China.
² School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China.

Abstract

Bromhexine is an expectorant drug repurposing as a TMPRSS2 inhibitor, which has also been proposed for potential treatment in COVID-19 infection. Multicomponent crystal strategy has been applied in bromhexine to improve its poor solubility, which limits its bioavailability and efficacy. A new bromhexine crystal and its fumarate salt crystal have been successfully obtained by slow evaporation technique. Both compounds have been characterized by X-ray single-crystal diffraction, TGA and FT-IR spectroscopy. Hirshfeld surface analysis has been carried out to further quantify the patterns of intermolecular interactions. Compared with bromhexine, the multicomponent crystal with pharmaceutically acceptable conformer of fumaric acid shows improved thermal stability and solubility in water.

Keywords: Bromhexine; Crystal structure; Hirshfeld surface; Multicomponent crystal; Salt; Solubility.