摘要
Polymorph screening is currently one of the most important tasks for innovators and for generic companies from both pharmaceutical and intellectual property rights aspects. The hemihydrate form（Form Ⅰ） and formamide solvate（Form Ⅱ） of estradiol are isolated and prepared via systemic crystallization screening in this paper, and the formamide solvate form is reported for the first time. Both polymorphic forms were characterized by single-crystal X-ray structure analysis（SXRD）, powder X-ray diffraction（PXRD）, and thermal analysis（TGA and DSC）. The PXRD experiments indicate that the samples in this study are the pure polymorphic forms via comparing the patterns with the simulated ones. The stability and equilibrium solubility data of the solid-state phase were also examined in order to check the impact of the differences observed in their crystalline structures. It has been found that Forms I and II are of conformational polymorph and Form II is the more thermodynamically stable solid form, while Form I possesses higher solubility, indicating its possibility as an alternate solid form for its further solid formulation development if necessary.
Polymorph screening is currently one of the most important tasks for innovators and for generic companies from both pharmaceutical and intellectual property rights aspects. The hemihydrate form（Form Ⅰ） and formamide solvate（Form Ⅱ） of estradiol are isolated and prepared via systemic crystallization screening in this paper, and the formamide solvate form is reported for the first time. Both polymorphic forms were characterized by single-crystal X-ray structure analysis（SXRD）, powder X-ray diffraction（PXRD）, and thermal analysis（TGA and DSC）. The PXRD experiments indicate that the samples in this study are the pure polymorphic forms via comparing the patterns with the simulated ones. The stability and equilibrium solubility data of the solid-state phase were also examined in order to check the impact of the differences observed in their crystalline structures. It has been found that Forms I and II are of conformational polymorph and Form II is the more thermodynamically stable solid form, while Form I possesses higher solubility, indicating its possibility as an alternate solid form for its further solid formulation development if necessary.
基金
supported by National Key R&D Program of China(No.2016YFC1000901)
the Postdoctoral Innovation Fund of National Research Institute for Family Planning(No.KYS[2017]BSHCX001)
