cocrystallizes

Co-crystallization is the process by which two or more molecular species form a crystalline material in a definite stoichiometric ratio, producing a co-crystal. In a typical co-crystal, the components retain their individual chemical identities but are held together in the crystal lattice by non-covalent interactions such as hydrogen bonding, halogen bonding, π–π stacking, and van der Waals forces.

Coformers, the partner molecules in a co-crystal, are usually solids at room temperature and chosen to modify the properties of the primary compound. The motivation for forming co-crystals includes improving solubility and dissolution rate, enhancing stability, modifying melting point, adjusting mechanical properties, or changing taste and handling characteristics. Co-crystals are of particular interest in pharmaceuticals for altering bioavailability without changing the molecular structure of the active ingredient.

Formation methods for co-crystals are diverse and include solution crystallization, slurry crystallization, solvent-assisted grinding (a mechanochemical approach), neat grinding, and anti-solvent crystallization. They may also be produced via vapor-assisted techniques or in situ crystallization during processing.

Characterization typically involves single-crystal X-ray diffraction to determine structure, powder X-ray diffraction to confirm phase purity, and thermal analyses such as differential scanning calorimetry and thermogravimetric analysis. Spectroscopic methods and elemental analysis help verify composition and stoichiometry.

Co-crystallization is distinct from salt formation, where proton transfer yields ionic species. In practice, the boundary can be nuanced, with some systems exhibiting features of both. Researchers often screen many potential coformers to identify viable and useful co-crystals.