晶型对枸橼酸托法替布原料药理化性质的影响  

Effect of Crystal Form on Physicochemical Properties of Tofacitib Citrate in Bulk Forms

作　　者：王燕[1,2] 牟伊 文帅 李幸 赵耀 王东凯 WANG Yan;MOU Yi;WEN Shuai;LI Xing;ZHAO Yao;WANG Dongkai(School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110122;College of Medicine and Chemical Engineering,TaizhouUniversity,Taizhou225300)

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110122 [2]泰州学院医药与化学化工学院,江苏泰州225300

出　　处：《中国医药工业杂志》2025年第1期89-95,共7页Chinese Journal of Pharmaceuticals

基　　金：2022年泰州市科技支撑计划(社会发展)项目(SSF20220050);江苏省高校自然科学研究重大项目(24KJA350004)。

摘　　要：研究了晶型对枸橼酸托法替布(1)原料药理化性质的影响。利用溶剂结晶法制备得到了2种晶型(晶型Ⅰ、晶型Ⅱ)的1,并通过PXRD、DSC/TGA及FT-IR进行表征,测定其粒度分布、平衡溶解度及流动性。结果显示,晶型Ⅰ的PXRD及FT-IR谱图与原研专利报道一致,DSC/TGA曲线略有差异,而晶型Ⅱ的PXRD、FT-IR谱图及DSC/TGA曲线和晶型Ⅰ存在明显差异;2种晶型的平衡溶解度差别不大,均呈现显著的pH依赖性,但晶型Ⅱ的溶解速率明显小于晶型Ⅰ;晶型Ⅱ粒径明显大于晶型Ⅰ,流动性较晶型Ⅰ好。该研究制得的新晶型(晶型Ⅱ)在缓控释制剂的开发中可能具有较好的应用前景。The effect of crystal form on the physicochemical properties of tofacitib citrate(1) in bulk forms were studied. Two kinds of 1 crystal(form Ⅰ and form Ⅱ) were prepared by solvent crystallization method. They were characterized by PXRD, DSC/TGA and FT-IR, and their particle size distribution, equilibrium solubility and fluidity were determined. The results showed that PXRD pattern and FT-IR spectrum of form Ⅰ were consistent with those reported in the original patent while the DSC/TGA curves were slightly different, but the PXRD pattern, FT-IR spectrum and DSC/TGA curves of form Ⅱ were significantly different from those of form Ⅰ. The equilibrium solubilities of form Ⅰ and form Ⅱshowed a significant pH dependence while the dissolution rate of form Ⅱ was significantly lower than that of form Ⅰ. In addition, the particle size of form Ⅱ was obviously larger than that of form Ⅰ, and the fluidity of form Ⅱ was better than that of form Ⅰ. This research indicated that the new crystal type(form Ⅱ) of 1 might have a good application prospect in the development of sustained-release preparations.

关 键 词：枸橼酸托法替布 类风湿性关节炎 多晶型表征 溶解性 粒径 流动性 

分 类 号：R917[医药卫生—药物分析学] O742.4[医药卫生—药学]