Cavatur R K, Suryanarayanan R
College of Pharmacy, University of Minnesota, Minneapolis 55455, USA.
Pharm Res. 1998 Feb;15(2):194-9. doi: 10.1023/a:1011950131312.
A low temperature X-ray powder diffractometric (XRD) technique has been developed which permits in situ characterization of the solid-state of solutes in frozen aqueous solutions.
A variable temperature stage, with a working temperature range of -190 to 300 degrees C, was attached to a wide-angle XRD. The stage was calibrated with a sodium chloride-water binary system.
When aqueous nafcillin sodium solution (22% w/w) was frozen, eutectic crystallization of the solute was not observed. However, annealing at -4 degrees C, caused crystallization of the solute. With increasing annealing time, there was a progressive increase in the crystallinity of the solute. Studies were carried out with sodium nafcillin solutions ranging in concentration from 20 to 50% w/w. The solid-state of the phase crystallizing from solution was independent of the solute concentration. Next, solutions of mono- and disodium hydrogen phosphate were individually frozen. Only the latter crystallized as the dodecahydrate (Na2HPO4.12H2O). However when an aqueous buffer mixture of mono- and disodium hydrogen phosphate was frozen, the former inhibited the crystallization of the latter.
Since freezing of solutions is the first step in lyophilization, the XRD technique can provide a mechanistic understanding of the alterations in solid-state that occur during freeze-drying. DSC has so far been the technique of choice to study frozen systems. The advantage of XRD is that it not only permits unambiguous identification of the crystalline solid phase(s), but it also provides information about the degree of crystallinity. While overlapping thermal events are difficult to interpret in DSC, XRD does not suffer from such a limitation.
已开发出一种低温X射线粉末衍射（XRD）技术，可对冷冻水溶液中溶质的固态进行原位表征。
将工作温度范围为-190至300摄氏度的可变温度台连接到广角XRD上。该温度台用氯化钠-水二元体系进行校准。
当冷冻22%（w/w）的萘夫西林钠水溶液时，未观察到溶质的共晶结晶。然而，在-4摄氏度下退火会导致溶质结晶。随着退火时间的增加，溶质的结晶度逐渐增加。对浓度范围为20%至50%（w/w）的萘夫西林钠溶液进行了研究。从溶液中结晶的相的固态与溶质浓度无关。接下来，分别冷冻磷酸氢二钠和磷酸氢二钠二水合物的溶液。只有后者结晶为十二水合物（Na2HPO4·12H2O）。然而，当冷冻磷酸氢二钠和磷酸氢二钠的水性缓冲混合物时，前者会抑制后者的结晶。
由于溶液冷冻是冻干的第一步，XRD技术可以提供对冻干过程中发生的固态变化的机理理解。到目前为止，DSC一直是研究冷冻系统的首选技术。XRD的优点是它不仅可以明确鉴定结晶固相，还可以提供有关结晶度的信息。虽然DSC中重叠的热事件难以解释，但XRD不存在这样的限制。
