Investigation of the solid forms of deferasirox: Solvate, co-crystal, and amorphous form

Abstract

Deferasirox (DFX) is an oral iron chelator. This study prepared and characterized five solid forms of DFX including monohydrate (DFX-H2O), dimethylformamide solvate (DFX-DMF), two co-crystals of DFX and isonicotinamide (INA) (DFX-INA and DFX-2INA), and amorphous DFX. Single crystals of DFX-H2O, DFX-DMF, DFX-INA, and DFX-2INA were obtained through solvent crystallization, and their structures were determined by single-crystal X-ray diffraction analysis. DFX-H2O, DFX-DMF, DFX-INA, and DFX-2INA were all monoclinic with P21/c, P21/c, P21/c, and C2/c space groups, respectively. In the four solid forms, the DFX molecule always maintained an S(6) ring motif, and its carboxylic acid moiety easily formed hydrogen bonds with the solvent or INA molecules. Solid forms were preliminarily estimated by stability and in vitro dissolution tests. DFX-INA and amorphous DFX showed good stability under ambient conditions and better dissolution characteristic compared with commercial DFX in phosphate buffer medium (pH 6.8). Thus, DFX-INA and amorphous DFX exhibited potential as preponderant solid forms of DFX for drug development.