Glycine Crystallization During Freezing: The Effects of Salt Form, pH, and Ionic Strength
- 1 January 1995
- journal article
- Published by Springer Science and Business Media LLC in Pharmaceutical Research
- Vol. 12 (10), 1457-1461
- https://doi.org/10.1023/a:1016223101872
Abstract
Purpose. The purpose of the study is to characterize glycine crystallization during freezing of aqueous solutions as a function of the glycine salt form (i.e., neutral glycine, glycine hydrochloride, and sodium glycinate), pH, and ionic strength. Methods. Crystallization was studied by thermal analysis, microscopy, x-ray diffraction, and pulsed Fourier transform nmr spectroscopy. Results. A solution of neutral glycine with no additives undergoes rapid secondary crystallization during freezing, forming the β polymorph, with a eutectic melting temperature of −3.4°C. Glycine hydrochloride solutions undergo secondary crystallization relatively slowly, and the eutectic melting temperature is −28°C. Sodium glycinate crystallizes from frozen solution at an intermediate rate, forming a eutectic mixture with a melting temperature of −17.8°C. Where secondary crystallization does not occur rapidly, a complex glass transition is observed in the −70° to − 85°C temperature range in the DSC thermograms of all systems studied. Rates of secondary crystallization and the type of crystal formed are influenced by solution pH relative the the pKs of glycine, and also by the change in ionic strength caused by adjustment of pH. Increased ionic strength significantly slows the crystallization of neutral glycine and promotes formation of the γ polymorph. Thermal treatment or extended holding times during the freezing process may be necessary in order to promote secondary crystallization and prevent collapse during freeze drying. Conclusions. The results underscore the importance of recognizing that seemingly minor changes in formulation conditions can have profound effects on the physical chemistry of freezing and freeze drying.Keywords
This publication has 7 references indexed in Scilit:
- Electrolyte-Induced Changes in Glass Transition Temperatures of Freeze-Concentrated SolutesPharmaceutical Research, 1995
- Effect of Mannitol Crystallinity on the Stabilization of Enzymes during Freeze-Drying.CHEMICAL & PHARMACEUTICAL BULLETIN, 1994
- Measurement of Glass Transition Temperatures of Freeze-Concentrated Solutes by Differential Scanning CalorimetryPharmaceutical Research, 1994
- An Improved Microscope Stage for Direct Observation of Freezing and Freeze DryingPharmaceutical Research, 1994
- Decreased Protein-Stabilizing Effects of Cryoprotectants Due to CrystallizationPharmaceutical Research, 1993
- The Effects of Formulation Variables on the Stability of Freeze-Dried Human Growth HormonePharmaceutical Research, 1991
- Inhibition and Reversal of Aggregation of Immunoglobulin G by Freezing.Acta Chemica Scandinavica, 1968