pH-dependent oiling-out during the polymorph transformation of disodium guanosine 5′-monophosphate

Oiling-out occurs frequently in industrial crystallization and strongly influences the morphology and quality of crystals. In this study, the influence of oiling-out with higher pH during the polymorph transformation of disodium guanosine 5-monophosphate (5'-GMNa(2)) on a water-isopropanol system was investigated. A ternary phase diagram with different pH and temperature values was studied using the focused beam reflectance measurement (FBRM) technique. In addition, the ion content in two separate liquid phases was determined. 5'-GMPNa(2) and 5'-GMPNa(3) were present in the mother liquid, and the proportion of 5'-GMPNa(3) increased with an increase in the pH of the mother liquid. From the thermogravimetry and differential scanning calorimetry (TG-DSC) data, it was observed that the 5'-GMPNa(3) molecules carried more hydrons than those escaping from the solution. The interaction energies of GMP (GMP(2-) and GMP(3-)) and H2O and IPA in the mixture solution were calculated using Gaussian and molecular dynamics (MD) simulations. The radial distribution function (RDF), weak interaction between the original GMP-H2O and final GMP-IPA, and the number density were calculated using MD simulations. The results indicated that GMP(3-) demonstrates stronger interaction with isopropanol under the solvation effect, which is in agreement with the experimental results. Furthermore, the mechanism of oiling-out brings more understanding and control in future industrial crystallization.