Insights into co-amorphous systems in therapeutic drug delivery

Co-amorphous (CAM) systems are promising drug-delivery systems in the arena of therapeutic drug delivery, addressing the poor aqueous solubility of drugs by enhancing solubility and thereby improving the oral bioavailability and therapeutic effect of the drug. A CAM system is a single-phase homogeneous blend of two or more low molecular weight molecules that can be drug-drug or drug-co-former, stabilized via intermolecular interactions, adding the benefit of thermodynamic stability. This review covers the fundamentals of CAM systems and recent advances in formulation development. In particular, we strive to address the theoretical, molecular, technical and biopharmaceutical aspects, advantages over polymeric amorphous solid dispersions, mechanisms of stabilization of amorphous forms, insights into unexplored in silico tools in excipient selection and regulatory viewpoints.