Phase transitions of glycine in frozen aqueous solutions and during freeze-drying

Purpose. To study the solid-state and phase transitions of glycine, (i) in frozen aqueous solutions, and (ii) during freeze-drying. Methods. X-ray powder diffractometry (XRD) and differential scanning calorimetry (DSC) were used to analyze the frozen systems. In situ freeze-drying in the sample chamber of the diffractometer enabled characterization of phase transitions during freeze-drying. Results. Transitions in frozen systems. Rapid (20°C/min) or slow (2°C/min) cooling of aqueous solutions of glycine (15% w/w) to -70°C resulted in crystallization of β-glycine. Annealing at -10°C led to an increase in the amount of the crystalline phase. When quench-cooled by immersing in liquid nitrogen, glycine formed an amorphous freeze-concentrate. On heating, crystallization of an unidentified phase of glycine occurred at ∼ -65°C which disappeared at ∼ -55°C, and the peaks of β-glycine appeared. Annealing caused a transition of β- to the γ- form. The extent of this conversion was a function of the annealing temperature. Slower cooling rates and annealing in frozen solutions increased the crystalline β-glycine content in the lyophile. Freeze-drying of quench-cooled solutions led to the formation of γ-glycine during primary drying resulting in a lyophile consisting of a mixture of β- and γ-glycine. The primary drying temperature as well as the initial solute concentration significantly influenced the solid-state of freeze-dried glycine only in quench-cooled systems. Conclusions. The cooling rate, annealing conditions and the primary drying temperature influenced the solid-state composition of freeze-dried glycine.