Binary and Ternary Phase Diagrams as Routes to Salt Discovery: Ephedrine and Pimelic Acid

Despite the commercial importance of molecular salts in pharmaceutical applications, there are few previous studies of their phase behavior in binary and ternary systems. In this current study salt formation is explored in both the binary system (1R,2S)-(−)-ephedrine/pimelic acid and in the related ternary system using water as a solvent. The utility of the binary phase diagram as an aid to full exploration of phase space is demonstrated, and this investigation makes use of both dry techniques (grinding) and crystallization from solutions to access possible solid phases. Inherent problems of isolating a metastable phase in the ternary system are revealed.