Performance and Characterization of Amorphous Solid Dispersions: An Overview

Abstract

In recent years the use of amorphous active pharmaceutical ingredients (API), adequately stabilized in a solid oral formulation, has attracted significant attention due to poor solubility of the crystalline forms of drug substances which often leads to inadequate bioavailability. These amorphous formulations, typically known as solid dispersions, exhibit higher solubility and dissolution rates than formulations prepared using the crystalline form of the API and hence can achieve higher bioavailability. However, since the amorphous form is inherently thermodynamically unstable as compared to the crystalline form, development of amorphous formulations also present unique challenges such as risk of crystallization of the API in the dosage form or during dissolution. In this chapter, we provide an overview of the oral drug absorption process, the formulation and physiological factors impacting drug absorption and the use of dimensionless numbers and absorption modeling in formulation selection. We provide an in-depth description of the concepts of supersaturation, crystallization, and speciation during dissolution, and their effect on product performance. Finally, solid-state failure modes such as crystallization and amorphous–amorphous phase separation in the dosage form are described along with techniques used to measure solid-state stability.