A comprehensive overview of the role of intermolecular interactions in amorphous solid dispersions

Abstract

Many recent studies have indicated that drug-polymer intermolecular interactions are an important aspect of amorphous solid dispersions (ASDs) and determine many of the properties of this type of formulations. In this review, a comprehensive overview is given of the latest insights with respect to intermolecular interactions in ASDs. The thermodynamic properties and theoretical considerations of the interactions are discussed, followed by a detailed and critical overview of the various solid-state analysis techniques used to probe interactions at the disposal of the formulation scientist. As the physical stability and the pharmaceutical performance of the ASD are its most crucial properties, the most recent understanding of the influence of drug-polymer interactions on these aspects is addressed as well. It is clear that intermolecular interactions may provide many advantages for ASDs but need to be weighed against the possible disadvantages. Further investigation into the interplay and trade-off between physical stability and dissolution properties is necessary in order to be able to take full advantage of the possible benefits of the interactions.