A review on design rules for formulating amorphous solid dispersions based on drug-polymer interactions in aqueous...

Amorphous solid dispersions (ASDs) are multi-component formulations in which a drug is molecularly dispersed in a carrier. ASDs undergo complex dissolution mechanisms to generate and sustain a supersaturated state of poorly soluble drugs. The link between enhanced solubility, supersaturation stability and drug-polymer interaction (DPI) is critical for the rational design of ASDs. The key mechanism responsible for a high bioavailability is the evolution of supersaturation during the dissolution of ASDs which is also the driving force for drug precipitation. A critical determinant of robust supersaturation generation and stability during dissolution is the molecular interaction between the drug and polymer. Characterization of DPI in a solution state is, however, challenging because of the poor hydrodynamic resolution of the techniques, traditionally used in solid-state analysis. Further, the dissolution conditions, such as the choice of buffer, pH and ionic strength may complicate the analyses and predictions. The role of DPI is a poorly understood aspect of ASD dissolution and therefore is an active area of research. DPI is critical for understanding the design rules for formulating an optimal ASD formulation. The review focuses on different aspects of DPI to stabilize the supersaturated state of a drug during the dissolution of ASDs.