Phase stability and successful isolation of a co-crystal by solution methods is influenced by solubility of API and co-former. The phase stability and solubility in a system can be visualized through ternary phase diagrams (TPDs). Depending on the conditions (solvent system, temperature) the co-crystal stability region can vary significantly. TPDs are an essential tool for solution-based methods and can be used to define the compositions of API, co-former and solvent where the co-crystal is stable at equilibrium. Boundaries of the co-crystal stability region can aid in defining safe operating parameters for a robust crystallization process and scale-up.
TPDs are developed through a combination of slurry experiments and solubility analysis. Solid phases are identified using analytical techniques such as X-ray powder diffraction while concentration of API and co-former are typically assessed by chromatography. The data are used to define phase stability boundaries, eutectic compositions, and develop a TPD which can be leveraged in co-crystallization process development. SSPI can not only help you screen for a co-crystal that may improve physiochemical properties and strengthen the IP of your drug, but we can also develop a process to allow the co-crystal to be scaled-up successfully.