Screening,Preparation,Characterization and Solubility of Polymorphic Forms of Ethinyl Estradiol

Ethinyl estradiol（EE） as a contraceptive,（17α）-19-nopregna-1,3,5-（10）-trien-20-yne-3,17-diol(formula: C;H;O;, molecular weight: 296.4, CAS number: 57-63-6), is known to have different pseudo-polymorphic forms. Some EE polymorphs have been synthesized by means of physical or chemical methods, characterized by X-ray powder diffraction（XRPD）, thermogravimetric（TG）, differential scanning calorimetry（DSC） and IR spectra. Dissolution profile was tested by high performance liquid chromatography（HPLC）. Meanwhile, the crystal structure of the new EE solvate（formamide） was characterized by single-crystal X-ray structure analysis（SXRD）. The results confirmed that EE existed polymorphism. Five crystal forms of EE were presented and two of them were reported firstly. Furthermore, five polymorphs’ dissolution curves were drawn and they could be identified by several analysis methods. Our study on polymorphs of EE could provide a variety of crystal material composition, preparation methods and solubility.