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.
Bibliographical noteFunding Information:
Partial financial support from the Parenteral Drug Association Foundation for Pharmaceutical Sciences is gratefully acknowledged. AP was partially supported by the ISWOP, University of Minnesota. We thank Mr. Rahul Surana and Dr. Raghu Cavatur for their valuable comments and Dr. Steven Nail for sharing with us, his manuscript under review.
Copyright 2008 Elsevier B.V., All rights reserved.
- Differential scanning calorimetry
- X-ray powder diffractometry