一种盐酸卡利拉嗪的新晶型

A New Polymorphic Form of Cariprazine Hydrochloride

发现并制备了盐酸卡利拉嗪的一种新晶型(命名为Ⅳ晶型)。利用粉末X射线衍射法、差示扫描量热法、热重法、衰减全反射傅里叶变换红外光谱法和扫描电子显微镜法分别对Ⅳ晶型和原研Ⅰ晶型进行表征分析,结果显示Ⅳ晶型与Ⅰ晶型存在明显的区别,差示扫描量热分析显示Ⅳ晶型在195℃转变为晶型Ⅰ;通过影响因素试验考察了2种晶型的稳定性,结果显示,Ⅳ晶型在高湿[相对湿度(90±5)%]条件下转变为Ⅰ晶型。试验结果表明Ⅳ晶型为Ⅰ晶型的亚稳晶型。通常认为亚稳晶型要比其相应的稳定晶型具有更好的溶解性。随后的溶解性试验也证实了Ⅳ晶型的水溶性较Ⅰ晶型更好。

A new polymorph of cariprazine hydrochloride（ named as form Ⅳ） was discovered and investigated. The form Ⅰ and Ⅳ were both characterized by powder X-ray diffraction, differential scanning calorimetry, thermal gravimetric analysis, attenuated total reflectance-fourier transform infrared spectroscopy and scanning electron microscopy. The results showed that form Ⅳ was significantly different from form I. The thermal gravimetric analysis showed that form Ⅳ would transform into form Ⅰ at around 195 ℃. Stress testing suggested that form Ⅳ would transform into form Ⅰ under high humidity condition [R.H.（90±5）%]. The above experimental data showed that form Ⅳ was a metastable crystal form. Metastable crystal form generally has better solubility than its corresponding stable form. Subsequent solubility measurement also verified that form Ⅳ could dissolve more in water than form Ⅰ.