Physicochemical properties of crystalline forms of ethynylestradiol solvates: comparison of thermal behavior with X-ray crystal structure.

Four crystalline forms of ethynylestradiol solvates were obtained from three solvents [acetonitrile (Form A), methanol (Form B), and chloroform saturated with water (Forms C and D)], and were characterized by X-ray powder patterns and thermal analyses. The crystal structures of Forms A, B, and C were further analyzed using the X-ray diffraction method, and the results are discussed in comparison with the thermal behavior of the crystalline forms. The steroid conformation of ethynylestradiol was rigid and no noticeable difference was observed among the solvated crystal structures; the molecular structure differed only in the orientation of the ethynyl group with respect to the steroid skeleton. The difference in the interaction mode between ethynylestradiol and the solvent molecules primarily discriminates the physicochemical properties.