Attainment of unstable β nucleation of glycine through novel swift cooling crystallization process

• β glycine was attained well above freezing point of water by swift cooling process.
• Nucleation behavior at different combinations of σ and stirring rates is revealed.
• β nucleation is observed at low σ levels in contrast to the existing scenario.
• Combinations at intermediate levels favor mixed β+α nucleation through SMPT.

The sudden cooling of mother liquor from high temperature to a temperature below the ambient through the recently introduced swift cooling crystallization process yielded the β nucleation of glycine even in the absence of anti-solvents and additives. Experiments were continued at different supersaturation and stirring levels. The nucleation matrix resulted out of these 135 experiments revealed that, even at lower supersaturation and lower stirring rates, the unstable β nucleation could be achieved. This attained result contrasts the existing reports in which β nucleation is achieved only at higher supersaturation levels. The intermediate supersaturation and stirring levels facilitate both the β and α nucleation through solution mediated phase transformation while the higher supersaturation and stirring levels facilitate only the α nucleation of glycine in the system. The swift cooling method adopted declines the energy barrier that inherently exists for β and enables its nucleation in the system. Analytically the nucleation parameters of β and α polymorphs were estimated based on Classical Nucleation Theory. Form of crystallization of the nucleated polymorphs of glycine was confirmed by powder x-ray diffraction analysis.