Creatine: Polymorphs Predicted and Found

Hydrate and anhydrate crystal structure prediction (CSP) of creatine (CTN), a heavily used, poorly water-soluble, zwitterionic compound, has enabled the finding and characterization of its anhydrate polymorphs, including the thermodynamic room temperature form. Crystal structures of the novel forms were determined by combining laboratory powder X-ray diffraction data and ab initio generated structures. The computational method not only revealed all experimental forms but also predicted the correct stability order, which was experimentally confirmed by measurements of the heat of hydration.
A computationally driven experimental search for anhydrate and hydrate solid forms of creatine enabled the finding and characterization (structure and stability) of its three polymorphs and the monohydrate. The computational method not only found the experimental forms but also correctly predicted the stability order, which was experimentally confirmed by measurements of the heat of hydration.