Furosemide Solvates: Can They Serve As Precursors to Different Polymorphs of Furosemide?

In the present work, four solvates of furosemide with tetrahydrofuran S­(THF), 1,4-dioxane S­(DIOX), N,N-dimethylformamide S­(DMF), and dimethylsulfoxide S­(DMSO) were crystallized, the crystal structures were solved for S­(THF), S­(DIOX), and S­(DMF). The existence of S­(THF) and S­(DMSO) was not reported before; for the previously known S­(DIOX) and S­(DMF), the crystal structures remained unsolved. The detailed structural analysis of furosemide containing crystal structures showed that the molecule of furosemide has a high conformational lability because of the rotations of the sulfamoyl and furanylmethylamino fragments. Some of the furosemide conformations were shown to be stabilized by the intramolecular N–H···Cl hydrogen bond. Desolvation of the four solvates was studied by TG and X-ray diffraction and was shown to give different products depending on the precursor and particle size: the desolvation of powder of S­(THF) and the large crystals of S­(THF), S­(DIOX), and S­(DMF) gives Form-III of furosemide, whereas powders of S­(DIOX), S­(DMF), and S­(DMSO) give Form-I.