Investigation of Amorphous Solid Dispersions for Solubility Enhancement of Poorly Water-soluble Drugs: Understanding the Effect of Material Properties on Amorphous Drug Crystallization and the Impact on Formulation Performance

The preparation of amorphous solid dispersions (ASDs) has enabled the development of oral dosage forms for many poorly water-soluble compounds. The aim of the work presented in this dissertation is to advance our understanding of ASDs, specifically their long-term stability with respect to crystallization and the implications of instability on product performance. Advancing knowledge in these areas is pivotal for the pharmaceutical industry and its efforts in drug discovery. Much of our understanding of ASD stability results from empirical or extrapolative models that have been applied to describe stability. Their application has been limited and they do not provide fundamental insights into the recrystallization process to aid in the rationale development in ASDs. Notably, they fail to consider supersaturation as the driving force for crystallization, diffusivity in viscous systems, and interfacial effects. The works presented in this dissertation model the mechanisms of crystal nucleation and growth in ASDs by incorporating these concepts, develop and apply characterization tools to determine critical model parameters, and study the effects of crystallization on product performance.Ph.D