盐酸美利曲辛多晶型的制备与表征

Preparation and Characterization of Melitracen Hydrochloride Polymorphs

制备了盐酸美利曲辛的7种晶型[Ⅰ、Ⅱ、A、B、C、D(一水合物)、E晶型],利用粉末X射线衍射法、差示扫描量热法、热重法、红外光谱法分别对7种晶型物质状态进行了表征分析;其中,A、B、C、D(一水合物)及E晶型为首次报道。通过影响因素试验探讨了7种晶型的稳定性与晶型转变规律,结果表明,Ⅰ、Ⅱ、A三种晶型为稳定晶型,B、C、E晶型在高湿[相对湿度(90±5)%]条件下转变为D晶型,B晶型在高温[(60±2)℃]条件下转变为E晶型,D晶型在高温[(60±2)℃]条件下失去结晶水转变为A晶型。本研究还对盐酸美利曲辛在无水乙醇中的不同结晶工艺条件下析出产物晶型的情况进行研究,结果表明搅拌速率、析晶温度对产物晶型有着重大的影响。

In this paper, the melitracen hydrochloride polymorphs [form Ⅰ, Ⅱ, A, B, C, D （monohydrate）, E] were prepared. The polymorphs were characterized by powder X-ray diffraction, differential scanning calorimetry, thermal gravimetric analysis and attenuated total reflectance-Fourier transform infrared spectroscopy. Among them, form A, B, C, D （monohydrate） and E were reported for the first time. Furthermore, the stability and the transformation were explored. Form Ⅰ, Ⅱand A were the stable forms. Form B, C and E were metastable forms which could transform to form D under high humidity condition [RH （90±5） % ]. Form B could transform to form E, and form D could transform to anhydrous form A at （60±2） ℃. In this article, the crystallization processes of melitracen hydrochloride in anhydrous ethanol were studied, and it was found that the stirring rate and crystallization temperature had significant influences on the form formation.