Approaches to Design of Pharmaceutical Cocrystals: A Review

Crystal engineering approaches have been found to increase the possibility of discovering the new solid forms. Cocrystals are solids that are crystalline single-phase materials composed of two or more different molecular and/or ionic compounds generally in a stoichiometric ratio which are neither solvates/hydrates nor simple salts. Cocrystals may be binary, ternary and quaternary based on the number of components present and may be ionic or polymorphic in nature because of the presence of components (i.e. ions or polymorphs) in the crystalline structure. Cocrystals offer a unique advantage of preserving the pharmacological properties of the Active Pharmaceutical Ingredient (API), and strive to add the improved physicochemical properties of the coformers. The main challenging step during the design of pharmaceutical cocrystals is the screening of coformers which are suitable with the API. In the development process of cocrystal, one of the approaches for coformer selection is based on trial and error. Many researchers have used some theoretical and experimental approaches for the selection of effective coformers in crystal engineering, for the design of pharmaceutical cocrystals. This review article briefly explains various types of cocrystals reported in the literature and crystal design approaches (such as hydrogen bonding propensity, pKa Rule, Cambridge structure database (CSD), Fabian's method and Hansen solubility parameters, with examples) for the selection of coformers which may be more selective, time-efficient and cost-effective.