Molecular complexes of drug combinations: A review of cocrystals, salts, coamorphous systems and amorphous solid dispersions

As the advancements in the medical technology and healthcare develop through the years, combinational therapy has evolved to be an important treatment modality in many disease settings, including cancer, cardiovascular disease and infectious diseases. In an effort to alleviate "pill burden" and improve patient compliance, fixed dose combinations (FDCs) have been developed to be used as effective therapeutics. Among all FDCs, the category of drug-drug molecular complexes has been proven an efficient methodology in designing and treating diseases, with many drugs being approved. Among all drug-drug molecular complexes, drug-drug cocrystals, salts, coamorphous systems and solid dispersions have been successfully developed and many have been approved by the FDA. In this review, we dwell deeply into the molecular mechanisms behind the different types of drug-drug molecular complexes, including the key functional groups involved in the intermolecular interactions, the applications of each category of molecular complexes, as well as the advantages and challenges thereof. This comprehensive review provides useful insights into the practical design and manufacture of drug-drug molecular complexes and points out the future direction for the development of new advantageous combinational therapies that benefit more patients.