Thermodynamic study on the amorphous form and crystalline hydrates using in situ raman and FBRM

Abstract

The solubilities and maximum supersaturation concentrations of an amorphous and the crystalline tetrahydrate and heptahydrate solids of disodium guanosine 5'-monophosphate (GMP) in water-methanol mixtures were measured in situ by Raman spectroscopy and focused beam reflectance measurement. The distinct Raman peaks of the amorphous form, crystalline hydrates, solution, and solvent were used for measurements of solubility and maximum supersaturation. Above 45 °C and at methanol fractions of 0.15–0.90, the tetrahydrate was the stable form, while below 40 °C and at methanol fractions of 0.15–0.60, the heptahydrate was the stable form. Especially, the tetrahydrate was stable in the methanol fraction > 0.7 at the temperature investigated. The solubility and supersaturated concentration values can be used to selectively produce amorphous, tetrahydrate, and heptahydrate solids of GMP by anti-solvent crystallization.