title: The construction, prediction and measurement of co-crystal ternary phase diagrams as a tool for solvent selection.
abstract: 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.
authors.affiliation: Department of Chemical Engineering, Institute of Chemical Technology Prague, Technická 5, 166 28 Prague 6, Czech Republic; Zentiva k.s., U kabelovny 130/22, 102 00 Prague 10, Czech Republic. Electronic address: holanj@vscht.cz.
authors.forename: Jan
authors.initials: J
authors.lastname: Holaň
authors.affiliation: Department of Chemical Engineering, Institute of Chemical Technology Prague, Technická 5, 166 28 Prague 6, Czech Republic.
authors.forename: František
authors.initials: F
authors.lastname: Stěpánek
authors.affiliation: Sanofi SA, 13 quai Jules Guesde, Vitry-Sur-Seine, 94403 Cedex, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Billot
authors.affiliation: Zentiva k.s., U kabelovny 130/22, 102 00 Prague 10, Czech Republic.
authors.forename: Luděk
authors.initials: L
authors.lastname: Ridvan
mesh_terms: D002151:Calorimetry; D019343:Citric Acid / Q000737:chemistry; D003460:Crystallization; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013696:Temperature
chemical_list: D004364:Pharmaceutical Preparations; D012997:Solvents; D019343:Citric Acid
keywords: Agomelatine; Co-crystal; DITA; Solubility; Ternary phase diagram