From Coformer to Cocrystal: A Review of Selection Approaches and Characterization in Drug Development

Abstract

Several active pharmaceutical ingredients (APIs) have poor physicochemical qualities and stability, which frequently limit the development of efficient pharmacological dosage forms. By creating multicomponent crystalline systems via non-covalent interactions between an API and an appropriate coformer, cocrystallization has become a cutting-edge crystal engineering technique to address these issues. Without changing the drug molecule’s chemical structure, this approach improves important characteristics like solubility, dissolution rate, stability, mechanical strength, and bioavailability. The basic ideas of pharmaceutical cocrystals are addressed in this review, with special attention paid to coformer selection criteria such as hydrogen bonding ability, pKa considerations, Hansen solubility parameters, supramolecular synthon concepts, structural database analysis and computational screening techniques like COSMO-RS. Additionally, important characterization techniques are described for verifying cocrystal formation and assessing structural and thermal properties, which include Fourier transform infrared spectroscopy and powder X-ray diffraction. Overall, pharmaceutical cocrystals offer a viable and affordable platform for enhancing therapeutic performance, especially for poorly soluble substances like BCS Class-II medications. It is anticipated that further developments in production technology, screening methods, and analytical approaches will broaden the uses of cocrystallization in contemporary drug development.