Detecting the phase transitions of tert-butanol hydrate by terahertz spectroscopy

The co-solvent system of tert-butanol and water is commonly employed in the field of freeze-drying pharmaceuticals. Investigating the phase composition and behavior of this system at low temperatures contributes to furthering its applications. In this study, THz-TDS was used to investigate the melting process of the frozen tert-butanol-water binary system for the first time. Utilizing the THz fingerprint peaks, we discovered that following the initial freezing, the system only formed metastable dihydrate tert-butanol, but near the melting point, it transformed into stable heptahydrate tert-butanol. This transition did not occur at high tert-butanol contents. Combining DFT calculations, all observed absorption peaks were attributed to the low-frequency vibration modes of each crystal. A phase diagram of the tert-butanol-water binary system was constructed based on the difference in absorbance intensity between the solid and liquid phases. The results demonstrate the potential of THz spectroscopy for applications in pharmaceutical freeze-drying.