Study On Polymorphism Of Ethinyl Estradiol

The in-depth study and discussion about crystallization thermodynamics,nucleation mechanism and thermal kinetics of polymorph were carried out in the work,and Ethinyl Estradiol was chosen as the research system,the specific research contents are as follows.Solution crystallization methods for different forms Ethinyl Estradiol were studied.The crystallization products were analyzed and characterized by using some equipments,such as XRPD,FT-IR,Raman,DSC and TG.And n new polymorph named form I of Ethinyl Estradiol was discovered.The solubility of form Ⅱ of Ethinyl Estradiol and Ethinyl Estradiol methanol solvent in methanol were measured by static balance method,and the data were correlated with Apelblat,λh and Vant’t Hoff empirical equation.It was found that the solubility increase with the temperature increasing,and the calculated values were good agreement with the experimental values,indicated that the empirical equation can be used to predict the solubility of Ethinyl Estradiol.Secondly,the enthalpy and entropy of dissolution of Ethinyl Estradiol form in methanol solvent were calculated by Van’t Hoff empirical equation.The metastable zone with and induction time of Ethinyl Estradiol in methanol solvent were measured by laser-scattering method.The effect of crystallization conditions,such as initial temperature,cooling rate and stirring speed,on metastable zone with and the effect of crystallization temperature and surpersaturation on induction were studied.The nucleation kinetics parameters were estimated based on the induction time data.The thermal decomposition processes of form Ⅱ of Ethinyl Estradiol and Ethinyl Estradiol methanol solvent were studied using thermogravimetry.The activation energy and pre-exponential factor of each process were calculated by model-free method(KAS equation).Then,the minimum deviation method was employed to determine the thermal analysis kinetic mechanism function.The effect of solution compition,temperature and initial concentration solution on the polymorphs of Ethinyl Estradiol was inverstigated.The preparation process of Ethinyl Estradiol methanol solvent was optimized.It was shown that in solvent mixture of methanol + water,the resulted crystal form is different at different solution composition.Cryatal form I of Ethinyl Estradiol was obtained in less methanol,and Ethinyl Estradiol methanol solvent was obtained in higher methanol.