Crystalline to amorphous transition of disodium hydrogen phosphate during primary drying

Purpose. To monitor the phase transitions during freeze-drying of disodium hydrogen phosphate. Methods. 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°C/min from room temperature to -70°C. It was then heated to -25°C and subjected to primary drying for 2 h at a chamber pressure of ∼100 mTorr, followed by secondary drying at -10°C. Results. In the frozen solution, disodium hydrogen phosphate had crystallized as the dodecahydrate (Na₂HPO₄·12H₂O) as was evident from its characteristic lines at ∼5.37, 4.27, and 2.81 Å. Primary drying for 2 h resulted in ice sublimation, and the complete disappearance of the dodecahydrate peaks. Conclusion. 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.