Polymer-Assisted Grinding, a Versatile Method for Polymorph Control of Cocrystallization
Despite the great interest that cocrystals are currently gaining for their application to the design of new supramolecular structures with desired functional properties, studies concerning new experimental strategies capable of controlling polymorphism phenomena of a given system are scarcely reported. We propose herein the use of polymer-assisted grinding (POLAG) as a new method for the selective control of the product polymorphic form in a mechanochemical cocrystallization reaction. Specifically, to the model system selected in this study formed by caffeine and glutaric acid, we demonstrate that the polymorphic outcome can be controlled by modifying the number of monomer units of the catalyst from the shortest dimer to a polymer with chains of approximately 1000 units. The characteristics of each polymorphic form were investigated by low-dose high-resolution TEM, and the mechanistic aspects of the cocrystal formation were studied through a series of ex situ and interconversion experiments. The results suggest that for this system the modification of the catalyst chain length and, consequently, modification of polarity drives cocrystal formation toward the more stable polymorph. The approach proposed in this paper can be readily applied to each system, where polarity is the main issue for polymorph control without the risk of solvate formation.
The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.
Citation : Hasa, D., Carlino, E. and Jones, W. (2016) Polymer-Assisted Grinding, a Versatile Method for Polymorph Control of Cocrystallization. Crystal Growth and Design, 16 (3), pp. 1772-1779
Research Institute : Leicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI)
Peer Reviewed : Yes
- Leicester School of Pharmacy