Chao R S, Vail K C
Product Control Division, Upjohn Company, Kalamazoo, Michigan 49001.
Pharm Res. 1987 Oct;4(5):429-32. doi: 10.1023/a:1016498731952.
Two polymorphs of 1,2-dihydro-6-neopentyl-2-oxonicotinic acid have been characterized by X-ray diffraction (XRD), infrared spectroscopy (IR), differential scanning calorimetry (DSC), and thermal (hot-stage) microscopy (HSM). In batch-scale preparation, form I was crystallized in ethanol-water (3:1), while form II was obtained by recrystallization from acetone-water (2:1). The melting points for forms I and II are 193 and 196 degrees C, respectively. Thermal studies (DSC and HSM) showed that form II melts at 196 degrees C, while form I melts at 193 degrees C, immediately followed by a resolidification and remelt at 196 degrees C. The conversion of form II to form I was accomplished by recrystallization from ethanol or methanol, and the form I-to-form II transition was obtained by controlled heating of form I around 194 degrees C. Quantitative XRD was used to determine the polymorphic composition, with a detection limit of less than 1% of the minor form and a linearity of 0-10% form I in form II (correlation coefficient of 0.999).
通过X射线衍射（XRD）、红外光谱（IR）、差示扫描量热法（DSC）和热（热台）显微镜（HSM）对1,2 - 二氢 - 6 - 新戊基 - 2 - 氧代烟酸的两种多晶型物进行了表征。在间歇规模制备中，晶型I在乙醇 - 水（3:1）中结晶，而晶型II是通过从丙酮 - 水（2:1）中重结晶获得的。晶型I和II的熔点分别为193℃和196℃。热学研究（DSC和HSM）表明，晶型II在196℃熔化，而晶型I在193℃熔化，随后立即重新固化并在196℃再次熔化。通过从乙醇或甲醇中重结晶实现晶型II向晶型I的转变，通过在194℃左右对晶型I进行控制加热获得晶型I向晶型II的转变。使用定量XRD来确定多晶型物组成，次要晶型的检测限小于1%，在晶型II中晶型I的线性范围为0 - 10%（相关系数为0.999）。
