A classical chiral resolution in which two enantiomers are separated via crystallization of a diastereomeric salt is a common method to achieve the required enantiopurity of a pharmaceutical compound. Of the three types of chiral systems (racemate, conglomerate mixture, and pseudo-racemate or solid solution), solid solutions are an infrequent and interesting case in which the undesired compound is incorporated in the crystal lattice of the desired compound, non-stoichiometrically, without changing the structure of the crystal lattice. In this work we present a methodology for characterizing the ternary phase behavior of a solid solution system, encompassing both an experimental workflow and a computational method for construction of a ternary phase diagram. We use a case study of a synthetic intermediate in our portfolio to illustrate the methodology, as well as highlight additional processing considerations including impurity rejection and compound stability, to enable a robust scale-up.
