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.

Improved physico-chemical properties by co-crystallization:

• Solubility
• Stability
• Taste masking
• Dissolution profile
• Bioavailability
• Melting point

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.