目的 研究低鈉血癥治療藥物托伐普坦的晶型特征。方法 采用蒸發(fā)結(jié)晶、溶析結(jié)晶、研磨轉(zhuǎn)晶等方法對(duì)托伐普坦進(jìn)行晶型制備篩選；采用粉末X射線衍射分析（PXRD）、差示掃描量熱分析（DSC）、紅外光譜分析（IR）、熱重–差熱分析（TG-DTA）以及單晶X射線衍射分析（SXRD）技術(shù)對(duì)制備得到的托伐普坦晶型樣品進(jìn)行表征；采用研磨、加熱、加壓和混懸方法對(duì)無水晶型進(jìn)行轉(zhuǎn)晶行為研究；此外，還對(duì)各種晶型進(jìn)行了溶解性質(zhì)研究。結(jié)果 通過上述制備方法獲得了托伐普坦的4種晶型狀態(tài)Ⅰ、Ⅱ、Ⅲ和Ⅳ型。其中Ⅰ型為無水晶型，Ⅱ型為溶劑化物，Ⅲ型為半水合物，Ⅳ型為無定型。Ⅰ、Ⅳ型在特定的條件下可以相互轉(zhuǎn)化。結(jié)論 采用PXRD、DSC和TG-DTA技術(shù)可實(shí)現(xiàn)4種晶型的直觀、快速、準(zhǔn)確鑒別。Ⅰ～Ⅳ型托伐普坦的理化性質(zhì)及穩(wěn)定性存在明顯差異，其中Ⅳ型為熱力學(xué)不穩(wěn)定晶型，溶解性最好，而Ⅰ型最穩(wěn)定。

Objective To study the polymorphic characteristics of tolvaptan for the treatment of hyponatremia. Methods Polymorph screening of the compound was carried out in this study. Polymorphs of tolvaptan were prepared by evaporative crystallization, antisolvent crystallization and other polymorph transformation methods such as grinding, and were characterized by powder X ray diffraction (PXRD), differential scanning calorimetry (DSC), infrared spectrometry (IR), thermogravimetric analysis coupled with differential thermal analysis (TG-DTA) and single crystal X ray diffraction analysis (SXRD). Grinding, heating, pressurizing and suspension methods were selected for studying polymorph transformation behavior of type I, and the dissolution properties of different polymorphs were also studied. Results It was found that tolvaptan obtained by the above methods existed four kinds of polymorphic state types I－IV. Among which, type I was anhydrous, type II was solvate, type III was semi-hydrate and type IV was amorphous. Types I and IV could be transformed into each other under certain conditions. Conclusion This study indicates that PXRD, DSC and TG-DTA could be used to identify the four kinds of tolvaptan polymorphs intuitively, rapidly and accurately. There are obvious differences in physicochemical properties and stability of different polymorphs, wherein type IV is thermodynamically unstable polymorph with best solubility, while type I is the most stable one.