Drug release from pharmaceutical co-crystals: Are therapeutic and safety properties of active pharmaceutical substances retained?

Co-crystallization of APIs can improve their solubility and permeability without changing their molecular structure, often obtaining increased oral bioavailability. On the other hand, we have evidenced that biological properties of co-crystals can be strongly different with respect to those of their parent physical mixture, probably due to different molecular aggregations that can differently interact with the membrane protein of cells such as transporters or tight junctions. Appropriate investigations seem therefore necessary to evaluate safety and therapeutics of co-crystals.