A mechanistic review on the dissolution phase behavior and supersaturation stabilization of amorphous solid dispersions.

Amorphous solid dispersion (ASD) technology is an attractive formulation approach for poorly soluble drugs because of the supersaturated state acquired during its dissolution. The high thermodynamic activity of the supersaturated state of the drug is also a driver for the enhanced absorptive flux across a membrane. However, this advantage can easily be lost due to the inherent instability of supersaturation, causing drug precipitation. Stabilizing the supersaturated state during the dissolution of ASD for the relevant absorption time frame is a challenging area in formulation research. Stabilizing the supersaturated state by using polymeric excipients and understanding the phase behavior of drugs during dissolution are required for the optimal performance of ASD formulations. A number of confounding kinetic, formulation and physiological factors can influence the evolution of supersaturation and phase changes during dissolution of ASDs. The review highlights the complex nature of dissolution of ASDs and the need of biorelevant dissolution for proper risk assessment and optimizing formulation development.