- 2:10 PM

Making Co-Crystals the Utility of Ternary Phase Diagrams

Renato A. Chiarella1, Roger J. Davey2, and Matthew L. Peterson1. (1) TransForm Pharmaceuticals, 29 Hartwell Av, Lexington, MA 02139, (2) University of Manchester, PO Box 88, Manchester, M60 1QD, United Kingdom

Co-crystal formation with active pharmaceutical ingredients has recently been considered an effective alternative to control the physical properties of a drug. Although several studies have been carried out on solvent-drop grinding as a means of co-crystal formation, little is available on the use of solid-liquid equilibrium measurements for co-crystal crystallization design.

A model system, nicotinamide and trans-cinnamic acid, is herein used to illustrate the challenges of solid phase discovery and control in a polymorphic co-crystal system. Crystallization of the stable and metastable co-crystal solid phases from solution, as well as through other techniques, is explored. Three component phase diagrams are presented to aid crystallization process design for scale-up.