摘要
采用溶液结晶法制备了由一分子异烟酰胺和一分子阿昔莫司组成的阿昔莫司-异烟酰胺共晶。将异烟酰胺和阿昔莫司在65℃条件下加热溶于甲醇,将溶清液趁热过滤,以500 r/min搅拌1 h,缓慢降温(0.2℃/min)至室温,析晶36 h,析出白色细针状晶体,抽滤干燥,即获得阿昔莫司-异烟酰胺共晶。应用单晶X射线衍射(SCXRD)、X射线粉末衍射(XRPD)、同步热分析(TGA/DSC)对阿昔莫司-异烟酰胺共晶进行了结构表征,并对其稳定性、溶解度以及药效等性质进行了研究。结果显示,共晶在不同pH值介质中的溶解度是阿昔莫司的2倍。大鼠的降血脂试验中,相对于与模型组,共晶组和阳性对照(乐知苹)组大鼠血清中甘油三酯、胆固醇、低密度脂蛋白水平明显下降;共晶组和阳性对照组间则无显著差异(P>0.05)。
Acipimox-isonicotinamide cocrystal, which was composed of a molecule isonicotinamide and a molecule acipimox, was prepared by solution crystallization. Acipimox and isonicotinamide were respectively dissolved in methanol at 65 ℃, then filtering and mixing under rotation (500 r/min) at 65 ℃ for 1 h. And then, the mixture was slowly cooled (0.2 ℃/min) to room temperature. After crystallization for 36 h, the white needle crystals were precipitated, the acipimox-isonicotinamide co-crystal was obtained through filtering and drying. The structure of cocrystals was characterized by single crystal X-ray diffraction (SCXRD), powder X-ray diffraction (XRPD), synchronous thermal analysis (TGA/DSC), respectively. The stability and solubility of the co-crystal were also assessed. The results showed that the solubilities of co-crystal in various pH solutions were increased to two times as compared with acipimox. The results of anti-hypercholesterolemic evaluation showed that compared with the model group, the serum levels of triglyceride, total cholesterol, low density lipoprotein in rats were obviously decreased in positive control (acipimox capsules, Olbetam) group and co-crystal group;while there were no significant differences between the positive control group and co-crystal group (P>0.05).
作者
郭立红
夏祥来
翟立海
张贵民
GUO Lihong;XIA Xianglai;ZHAI Lihai;ZHANG Guimin(Liman Pharmaceutical Group Co., Ltd., Linyi 273400;National Engineering and Technology, Research Center of Chirality Pharmaceutical, Linyi 273400)
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2019年第4期430-435,455,共7页
Chinese Journal of Pharmaceuticals
关键词
阿昔莫司-异烟酰胺
共晶
结构表征
稳定性
溶解度
药效
acipimox-isonicotinamidc
co-crystal
structural characterization
stability
solubility
pharmacodynamics
