Pyne Abira, Chatterjee Koustuv, Suryanarayanan Raj
College of Pharmacy, 308 Harvard St. S.E., University of Minnesota, Minneapolis, Minnesota 55455, USA.
Pharm Res. 2003 May;20(5):802-3. doi: 10.1023/a:1023445905372.
To monitor the phase transitions during freeze-drying of disodium hydrogen phosphate.
The variable temperature sample stage of the X-ray diffractometer (XRD) was attached to a vacuum pump, which enabled the entire freeze-drying process to be carried out in the sample chamber. The phase transitions during the freeze-drying cycle were monitored in real time by XRD. Aqueous buffer solution (containing disodium hydrogen phosphate and sodium dihydrogen phosphate) was cooled at 2 degrees C/min from room temperature to -70 degrees C. It was then heated to -25 degrees C and subjected to primary drying for 2 h at a chamber pressure of approximately 100 mTorr, followed by secondary drying at -10 degrees C.
In the frozen solution, disodium hydrogen phosphate had crystallized as the dodecahydrate (Na2HPO4 x 12H2O) as was evident from its characteristic lines at approximately 5.37, 4.27, and 2.81 angstroms. Primary drying for 2 h resulted in ice sublimation, and the complete disappearance of the dodecahydrate peaks.
The dehydration of the crystalline dodecahydrate resulted in an amorphous anhydrate. Thus the amorphous nature of the end product is a result of phase transitions during the process and do not reflect the solid-state of the ingredients during the entire process.
监测磷酸氢二钠冻干过程中的相变。
将X射线衍射仪(XRD)的可变温度样品台连接到真空泵上,使整个冻干过程能够在样品室中进行。通过XRD实时监测冻干循环过程中的相变。将缓冲水溶液(含有磷酸氢二钠和磷酸二氢钠)以2℃/分钟的速度从室温冷却至-70℃。然后将其加热至-25℃,并在腔室压力约为100毫托的条件下进行2小时的一次干燥,随后在-10℃下进行二次干燥。
在冷冻溶液中,磷酸氢二钠已结晶为十二水合物(Na2HPO4·12H2O),从其在约5.37、4.27和2.81埃处的特征谱线可以明显看出。2小时的一次干燥导致冰升华,十二水合物峰完全消失。
结晶十二水合物的脱水产生了无定形无水物。因此,最终产品的无定形性质是该过程中相变的结果,并不反映整个过程中成分的固态状态。