The construction, prediction and measurement of co-crystal ternary phase diagrams as a tool for solvent selection

• Published in: European journal of pharmaceutical sciences 2014-10, Vol.63, p.124-131
• Main Authors: Holaň, Jan, Štěpánek, František, Billot, Pascal, Ridvan, Luděk
• Format: Article
• Language: English
• Subjects: Agomelatine; Calorimetry; Citric Acid - chemistry; Co-crystal; Crystallization; DITA; Pharmaceutical Preparations - chemistry; Solubility; Solvents - chemistry; Temperature; Ternary phase diagram
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2014.06.017

[Display omitted] Many active pharmaceutical ingredients (APIs) are poorly soluble and therefore poorly bioavailable. In recent years, the advances in crystal engineering have motivated the research in the design of pharmaceutical co-crystals. This study examines the combination of solvent selection and co-crystal ternary phase diagram prediction on the basis of solubility measurements into a single methodology that can be integrated into the pharmaceutical process development workflow. Ternary diagrams constructed from agomelatine citric acid co-crystal solubility data were compared with those obtained by modern calorimetric method called discontinuous isoperibolic thermal analysis (DITA). A suitable solvent for the co-crystallization process has been chosen on the basis of agomelatine citric acid co-crystal solubility, which is connected to the yield of the crystallization process. Furthermore, the quality of final crystals from crystallization experiments was evaluated.