【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。更多还原

【Abstract】 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.更多还原