Screening for Co-crystals with a Solubility-Based Approach

Co-crystals are a form of crystal engineering that is gaining an increased level of interest across different industries. Co-crystals are a multicomponent complex, similar to salts, solvates and hydrates, where a second molecule is incorporated into the crystal lattice. However, unlike other complexes, the second molecule must be neutral and not a solvent.

 

 

 



When screening for co-crystals, chemical diversity is also key. Using the 16 parallel reactors of the Crystal16 instrument, you can test a wide diversity of crystallization conditions such as solvents and solvent mixtures, compound concentrations, co-formers, temperature profiles. However, conventional screening methods use stoichiometric quantities of the components and may miss a significant number of potential co-crystals. By making use of the solubility information of the individual components, it is possible to identify a concentration of the two components where the solubility of the co-crystal is the dominant factor, being 10°C greater than the solubility of the components. Collection of the solubility data used for this screening method can be done reliably, rapidly, and simply.

From the solubility curves obtained with the Crystal16 instrument, one may generate a Tclear for a sample consisting of the saturation concentrations of the individual components. If the solubility temperature of this mixture is greater than the individual components, it indicates the formation of a more stable less soluble form, a co-crystal. Further confirmation of co-crystal formation may be pursued by making use of secondary analysis such as single crystal XRD or a combination of analysis such as XRPD, DSC/TGMS.

 

Take the guess out of your experiments by making use of the Crystal16 instrument and a systematic solubility-based approach for your co-crystallization screens.

Click here for the application note for more details and references on this topic.
Click here for more information on salt formation.