Cocrystallizing

Cocrystallizing refers to the formation of a cocrystal, a crystalline material composed of two or more distinct molecular entities in a definite stoichiometric ratio. In most cases, one component is an active pharmaceutical ingredient (API) or another organic molecule, and the second is a coformer that participates through non-covalent interactions such as hydrogen bonding, pi–stacking, or van der Waals forces. Cocrystals differ from salts in that they are neutral solids held together by non-ionic intermolecular interactions rather than ionic bonds.

Coformers are typically solid, safe, and capable of forming stable networks with the API. Selection is guided by supramolecular design principles, such as matching hydrogen-bond donors and acceptors and avoiding proton transfer that would form a salt. The resulting cocrystal may modify properties like solubility, dissolution rate, stability, and mechanical behavior while preserving the API’s molecular identity.

Preparation methods include solution crystallization, where the API and coformer are co-dissolved and crystallized; solvent-assisted or neat grinding (mechanochemical synthesis); slurry crystallization; and anti-solvent crystallization. Other routes include twin-screw extrusion and other solid-state techniques. Conditions are chosen to favor cocrystal formation over homomeric crystallization.

Characterization uses techniques such as single-crystal X-ray diffraction and powder X-ray diffraction to determine structure and purity; differential scanning calorimetry and thermogravimetric analysis to evaluate thermal behavior; solid-state NMR and infrared spectroscopy to probe interactions. Cocrystals have applications in pharmaceuticals to tune solubility and bioavailability, as well as in agrochemicals and functional materials. Regulatory acceptance treats cocrystals as distinct solid forms; their status and patentability depend on jurisdiction and specific formulation.