Dissolution and Growth Kinetics and the Rate-Controlling Step in Transformation of Amorphous to Crystalline Phase Using Antisolvent Crystallization

Abstract

The kinetics of the formation of amorphous disodium guanosine 5′-monophosphate and its transformation to the heptahydrate phase were studied under various operating conditions using in situ Raman and focused beam reflectance measurement (FBRM). Supersaturation, solvent composition, feed concentration, addition rate, and viscosity were shown to affect the rate-determining steps of the transformation. The rate-controlling mechanisms in the overall kinetics have been confirmed. The observation of the slurry viscosity of the suspension of the amorphous phase shows the option to observe the phase transformation. The transformation process was affected by the dissolution, growth, and supersaturation in which the rate-controlling step was divided into two sections, such as the initial and later sections of the transformation. The overall rate constants were determined by combining the constants of the dissolution rate and the growth rates of each section. In situ Raman spectroscopy examination of the concentration of solution and solids can determine the rate-limiting processes during the transformation. The zero-order, first-order, and surface reaction equations as kinetic equations are highlighted and compared for the dissolution of the amorphous solids and the growth of the heptahydrate crystals. The dissolution of the amorphous (metastable form) and the growth of the heptahydrate (stable form) were found to be best fitted to the zero-order kinetic model. In particular, the variation of particle size distribution over time can give the rate-determining steps. These results suggest that the data measured by Raman spectroscopy and FBRM can be successfully coupled into a dissolution and growth model to further grasp and interpret the phase transformation. A dissolution rate-controlling step was dominated by a pattern in which both supersaturation and amorphous dissolution decreased simultaneously, and the growth rate-controlling step was shown in a pattern in which either supersaturation or amorphous dissolution was constant. Furthermore, the growth of heptahydrate crystals at a viscosity of the suspension with the amorphous solids below 70 cp and the dissolution of the amorphous solids above it can be used as the key determinant. Using the method developed and the kinetic constants obtained in this work, it is possible to create an appropriate control strategy to produce the desired form in the final product.