Finding Conditions to Process Hydrate Crystals and Amorphous Solids of Disodium Guanosine 5′‐Monophosphate by an Antisolvent Crystallization Process

A screening of amorphous, heptahydrate, and tetrahydrate forms of disodium guanosine 5′‐monophosphate is investigated using an antisolvent crystallization process with the aim to selectively produce each solid form. The concentrations of the solution and solid forms are monitored by in situ Raman spectroscopy using a calibration tool. Particle sizes and particle counts are measured with elapsed time by a focal beam reflection measurement. Concentrations of amorphous and hydrates phases are determined using in‐line measurement techniques. The variables studied are temperature, initial concentration, addition rate, and solvent fraction. The results demonstrate that transformation from amorphous to hydrate forms consists of four stages, which are the nucleation of the amorphous form, predissolution of amorphous form, the nucleation of hydrate crystal and dissolution of amorphous solid, and the growth of hydrate crystal. The rate‐controlling step, in this case, is the dissolution of amorphous form. Transformation between heptahydrate to tetrahydrate crystals is a nucleation‐growth‐controlled step. It is possible to obtain selectively the solid forms of disodium guanosine 5′‐monophosphate by referring to the supersaturation and solubility data. The results demonstrate that amorphous–hydrate transformation consists of four stages, which are the nucleation of the amorphous form, pretransformation of the amorphous form, the nucleation of hydrate and dissolution of the amorphous form, and the growth of hydrate crystal. The rate‐controlling step is the dissolution of the amorphous form. The transformation between heptahydrate and tetrahydrate is a nucleation‐growth‐controlled step.