Abstract by Xuezhi Zhuo

Proteins have recently caught attention as potential excipients for amorphous solid dispersions (ASDs) to improve oral bioavailability of poorly water-soluble drugs. Notably, the thesis highlights whey protein isolates, particularly β-lactoglobulin (BLG), as promising candidates in amorphous stabilization, dissolution and solubility enhancement, achieving drug loadings of 50 wt% and higher. Consequently, this thesis investigates the mechanisms behind the stabilization of amorphous drugs in the solid state and the enhancement of their solubility in solution using BLG-based ASDs. Firstly, the dissolution performance of BLG-based ASDs is compared to more traditional polymer-based ASDs and nanocrystalline formulations. Secondly, the drug loading onto BLG and the resulting amorphous stabilization mechanisms is summarized. Thirdly, interactions between BLG and drug molecules in solution are described as the mechanisms governing the improvement of drug solubility. Lastly, we outline the impact of the spray drying process on the secondary structure of BLG, and the resulting differences in amorphous stabilization and drug dissolution performance between α-helix-rich and β-sheet-rich BLG-based ASDs. These findings advance the understanding of protein-based ASDs in pharmaceutical applications, particularly for improving drug solubility and stability.