Thermodynamic aspects of freeze-drying: A case study of an “organic solvent–water” system

Aqueous solutions of glycine and tetrahydrofuran (THF) were frozen under variable conditions and subsequently annealed. The phases that resulted from this process were studied by X-ray diffraction, DSC and cryotemperature SEM. Under conditions achieved in common laboratory freeze-dryers, the THF clathrate hydrate of cubic structure II was formed in near-quantitative yields. The temperature–composition state diagram for the THF–water–β-glycine systems suggests that the critical temperature of the primary drying stage is the temperature of the four-phase peritectic reaction (269 K), and not the temperature of the congruent melting of the THF hydrate in the THF–water system (278 K). Freeze-drying is shown to go much faster if aqueous solutions are substituted for THF–water solutions. This finding is of great importance for practical applications, including pharmaceutical drug formulation.