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.
- M. J. Akers, N. Milton, S. R. Byrn, and S. L. Nail. Glycine crystallization during freezing: The effects of salt form, pH and ionic strength. Pharm. Res. 12:1457-1461 (1995).
- E. Y. Shalaev, D. V. Malakhov, A. N. Kanev, V. I. Kosyakov, F. V. Tuzikov, N. A. Varaksin, and V. I. Vavilin. Study of the phase diagram water fraction of the system water-glycine-sucrose by DTA and X-ray diffraction methods. Thermochim. Acta 196:213-220 (1992).
- S. Chongpresart. Influence of drug polymorphism on the physical chemistry of freeze-drying, Ph.D. Thesis, Purdue University, 1998.
- R. Suryanarayanan. Powder X-ray diffractometry. In H. G. Brittain, (ed.), Physical Characterization of Pharmaceutical Solids, Marcel Dekker, New York, 1995, pp. 187-221.
- R. K. Cavatur and R. Suryanarayanan. Characterization of frozen aqueous solutions by low temperature X-ray powder diffractometry. Pharm. Res. 15:193-198 (1998).
- N. V. Phadnis and R. Suryanarayanan. Polymorphism in anhydrous theophylline-Implications on the dissolution rate of theophylline tablets. J. Pharm. Sci. 86:1256-1263 (1997).
- E. Y. Shalaev and P. L. Steponkus. Phase diagram of 1,2-dioleoylphosphatidylethanolamine (DOPE): Water system at subzero temperatures and at low water contents. Biochim. Biophys. Acta 1419:229-247 (1999).
- H. Sakai, H. Hosogai, T. Kawakita, K. Onuma, and K. Tsukamoyo. Transformation of a-glycine to g-glycine. J. Crystal Growth 116:421-426 (1992).
- W. Ostwald. Lehrbuch der Allgemeinen Chemie, 2; W. Engelmann, Leipzig, Germany, 1896.
- K. Kasraian, T. M. Spitznagel, J. A. Juneau, and K. Yim. Characterization of the sucrose/glycine/water system by differential scanning calorimetry and freeze-drying microscopy. Pharm. Dev. Technol. 3:233-239 (1998).
- J. F. Carpenter and B. S. Chang. Lyophilization of protein pharmaceuticals. In K. E. Avis and V. L. Wu (eds.), Biotechnology and Biopharmaceutical Manufacturing, Processing and Preservation, Interpharm Press, Buffalo Grove, 1996, pp. 199-264.
- R. K. Cavatur and R. Suryanarayanan. Characterization of phase transitions during freeze-drying by in situ X-ray powder diffractometry. Pharm. Dev. Tech. 3:579-586 (1998).
- S. L. Nail, L. M. Her, C. P. Proffitt, and L. L. Nail. Improved microscope stage for direct observation of freezing and freeze-drying. Pharm. Res. 11:1098-1100 (1994).
- L. A. Gatlin. Kinetics of phase transitions in frozen solutions. Devl. Biol. Std. 74:93-104 (1990).
- N. Milton and S. L. Nail. The crystallization kinetics of glycine hydrochloride from frozen solution. Cryo-lett. 18:335-342 (1997).
- Phase Transitions of Glycine in Frozen Aqueous Solutions and During Freeze-Drying
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