Grinding Method for Phase Transformation of Glycine.

Glycine had three polymorphs, two metastable phases (α-glycine, ß-glycine) and one stable phase (γ-glycine). However, the phase transformation of glycine from α-phase to γ-phase was well known as the kinetically unfavorable process. In this study, a simple and effective grinding method for phase transformation of glycine from α-phase to γ-phase is proposed. In an aqueous solution, α-glycine and γ-glycine had bulk solubilities of 180 and ∼172 g/L, respectively. According to the Ostwald-Freundlich equation, however, as the crystal size of α-glycine was reduced to ∼0.6 µm by grinding, the saturated concentration of α-glycine increased from 180 to 191 g/L. As long as the solution concentration exceeds a critical point (σ = 0.1), it can be possible to suddenly induce the nucleation of γ-glycine by grinding the α-glycine crystal in the solution. Subsequently, the complete transformation of α-phase to γ-phase was achieved without additives. Similarly, the grinding method was effective for producing the γ-glycine crystal in the cooling crystallization whereas the α-glycine crystal was always produced in the cooling crystallization without grinding. This study showed that physical grinding can effectively facilitate phase transformation by triggering the nucleation of stable polymorph.

Study of phase transformation of guanosine 5'-monophosphate in drowning-out crystallization.

The present study used a mechanistic approach to control the phase transformation of guanosine 5'-monophosphate (GMP) via the operating conditions of agitation and feed concentration during drowning-out crystallization. First, Fourier transform infrared and UV/vis spectrophotometry were successfully applied to monitor the mass fraction of GMP polymorphs (amorphous and hydrate crystalline GMPs) and GMP supersaturation, respectively, during the crystallization. The phase transformation of amorphous GMP into hydrate crystals was significantly influenced by the agitation, which promoted the mass transfer of GMP dissolution and growth. Therefore, the phase transformation was quickly finished when increasing the agitation speed. However, a high agitation caused breakage of the hydrate crystals, resulting in a reduced crystal size with a bimodal distribution. The phase transformation was also influenced by the GMP feed concentration, as the crystal growth was promoted and the crystal size increased when increasing the feed concentration up to 61 g/l. However, a further increase in the feed concentration caused secondary nucleation due to the induction of a high supersaturation level during the phase transformation, leading to a small crystal size with a bimodal distribution. In addition, the rectangular-shaped hydrate GMP crystals exhibited a higher growth rate in the b direction rather than the a direction. Therefore, the crystal morphology shifted from a long rectangle to a square when increasing the feed concentration.