coformer

A coformer's term is used in crystal engineering to denote a molecule that forms a co-crystal with another compound, typically an active pharmaceutical ingredient (API) or a functional material. In a co-crystal, the components are neutral and are linked by non-covalent interactions such as hydrogen bonding, π–π stacking, and electrostatic forces, with little or no proton transfer. This distinguishes co-crystals from salts.

Coformers are selected to modify the properties of the primary molecule. The goals often include improving solubility and dissolution rate, adjusting stability and hygroscopicity, and enhancing processability or taste. Because coformers are part of the solid form of a drug product, their safety and regulatory status are important considerations in development.

Selection and common examples: Coformers are usually small organic molecules bearing functional groups capable of hydrogen bonding, such as carboxylic acids, amides, amines, or alcohols. Widely used coformers include nicotinamide, isonicotinamide, saccharin, urea, glutaric acid, and citric acid. The choice depends on complementary functional groups and crystal packing opportunities with the API.

Formation and characterization: Co-crystals can be prepared by solvent crystallization, mechanical grinding (mechanochemical methods), slurry crystallization, or anti-solvent techniques. Characterization typically relies on single-crystal or powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and solubility or dissolution studies to confirm the co-crystal structure and properties.

Regulatory and practical considerations: Because coformers contribute to a drug's solid form and potential exposure, safety evaluation is required. Some coformers have GRAS status or are approved excipients, but regulatory assessments and quality control remain essential. Limitations include selective co-crystal formation and phase behavior that can complicate manufacturing.

See also: co-crystal, crystal engineering, solid form