Kinetics of glycine crystallization during freezing of sucrose/glycine excipient systems.

Isothermal calorimetry and low-field nuclear magnetic resonance were used to measure crystallization of glycine during annealing of glycine/sucrose mixtures, a commonly-used excipient system for freeze-dried proteins. Kinetics of crystallization of glycine were consistent between the two methods, although the NMR method was significantly more sensitive. By the calorimetric method used here, sensitivity was lost when the total solute concentration was below about 20% (w/v) and the relative glycine concentration below about 35% of the total solids. By the NMR method, total solute concentrations as low as 5% (w/v) could be studied. When the relative concentration of glycine is below about 30% of total solids, the time course of crystallization becomes excessively long for practical freeze-drying applications. A good fit of the crystallization data was obtained with the Johnson-Mehl-Avrami (JMA) equation. The Avrami exponent of 2.5 is consistent with diffusion-limited spherulitic growth of glycine.