Analysis of the Dissolution and Crystallization of Partly Immiscible Ternary Mixtures Using a Composite Sensor Array of In Situ ATR-FTIR, Laser Backscattering, and Imaging

The thermodynamic phase diagram of an agrochemical active ingredient (AI) in water and acetone was determined using an array of process analytical technology (PAT) tools and equilibrium experiments. This ternary system was found to separate into multiple liquid phases at certain temperatures and concentrations (oiling out). Furthermore, agglomeration of the solid particles was observed at specific conditions. Signals from laser backscattering, attenuated total reflection infrared spectroscopy, and in situ imaging were used to study oiling out and to understand the interactions among the different phases and how they affected the dynamics of dissolution and crystallization of the AI. Characterizing partly immiscible ternary mixtures is a challenging task due to the presence of multiple dispersed phases such as droplets, particles, and agglomerates that are difficult to discriminate using traditional analytical techniques. The approach proposed here combines and integrates signals from multiple complementary online measurements to understand and monitor such complex systems.