A Review on Pharmaceutical Cocrystals – Preparation, Characteristics and Applications

Cocrystals are defined as multicomponent crystalline materials composed of an active pharmaceutical ingredient (API) and one or more neutral coformers, held together through non-covalent interactions such as hydrogen bonding, π–π stacking, and van der Waals forces. Unlike salts or solvates, cocrystals retain the chemical identity of the API while offering a unique opportunity to modify its physicochemical properties without altering its pharmacological activity. This makes cocrystal engineering an attractive strategy in pharmaceutical development, particularly for improving drug solubility, dissolution rate, stability, and bioavailability. This review provides a comprehensive overview of the fundamental principles of cocrystal formation, including the selection criteria for suitable coformers and the role of supramolecular synthons in guiding crystal assembly. Various preparation techniques such as solvent evaporation, grinding, and slurry conversion are discussed, highlighting their advantages and limitations. In addition, a range of analytical techniques—including powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), and single-crystal X-ray diffraction (SCXRD)—are examined for their role in characterizing and confirming the formation of cocrystals. Overall, the strategic application of cocrystals represents a significant advancement in formulation science, offering a versatile platform to overcome challenges associated with poorly soluble or unstable drug molecules.