Jumping into metastable 1:1 urea-succinic acid cocrystal zone by freeze-drying

Aqueous solutions with molar ratios between urea and succinic acid from 0.3:1 to 3:1 were evaporated at room temperature, and products were pure or mixtures of stable 2:1 urea-succinic acid cocrystals, urea or succinic acid. By freeze-drying, metastable 1:1 urea-succinic acid cocrystal formed. The different mixtures of the 1:1 cocrystals reveal several "hidden" metastable zones in a ternary phase diagram of the 2:1 cocrystal. The formation of the 1:1 cocrystal indicated that the solution composition points in the phase diagram "jump" over the stable zone into the metastable zones

Jumping into metastable 1:1 urea-succinic acid cocrystal zone by freeze-drying

Aqueous solutions with molar ratios between urea and succinic acid from 0.3:1 to 3:1 were evaporated at room temperature, and products were pure or mixtures of stable 2:1 urea-succinic acid cocrystals, urea or succinic acid. By freeze-drying, metastable 1:1 urea-succinic acid cocrystal formed. The different mixtures of the 1:1 cocrystals reveal several "hidden" metastable zones in a ternary phase diagram of the 2:1 cocrystal. The formation of the 1:1 cocrystal indicated that the solution composition points in the phase diagram "jump" over the stable zone into the metastable zones

Cocrystallization of urea and succinic acid in “Nano-Crystallizer”

In the bulk scale of crystallization, urea-succinic acid (U-SA) cocrystals have been reported to only form stable 2:1 U-SA cocrystal, without any metastable 1:1 cocrystal, by slow evaporation and cooling crystallization in an aqueous solvent. In this work, cooling crystallization and evaporation crystallization were applied in nano-crystallizers, i.e. the nano-pores in controlled pore glass (CPG). It is the first time to demonstrate that, with confined solution, it is possible to produce and maintain metastable cocrystals during the slow crystallization process, indicating the strong influences of the confinement on the phase diagram and the thermodynamic properties of the nano-scale cocrystals. The influences of the urea and succinic acid concentration and the pore size of CPG on the polymorphs and melting point of the nanocrystal have been investigated. Further understanding of the mechanism may contribute to new methods for maintaining the unstable materials and discovering new forms of pharmaceutical compounds and materials

Cocrystallization of urea and succinic acid in “Nano-Crystallizer”

In the bulk scale of crystallization, urea-succinic acid (U-SA) cocrystals have been reported to only form stable 2:1 U-SA cocrystal, without any metastable 1:1 cocrystal, by slow evaporation and cooling crystallization in an aqueous solvent. In this work, cooling crystallization and evaporation crystallization were applied in nano-crystallizers, i.e. the nano-pores in controlled pore glass (CPG). It is the first time to demonstrate that, with confined solution, it is possible to produce and maintain metastable cocrystals during the slow crystallization process, indicating the strong influences of the confinement on the phase diagram and the thermodynamic properties of the nano-scale cocrystals. The influences of the urea and succinic acid concentration and the pore size of CPG on the polymorphs and melting point of the nanocrystal have been investigated. Further understanding of the mechanism may contribute to new methods for maintaining the unstable materials and discovering new forms of pharmaceutical compounds and materials