Professor Thomas Rades

The low water solubility of many low molecular weight drugs continues to be a challenge in the development of oral drug formulations since low water solubility can lead to low or variable bioavailability. Amongst the various enabling formulations that are conceived to tackle this challenge, a very promising approach to increase not only the dissolution rate but also the apparent solubility of drugs, is the conversion of the crystalline drug material into an amorphous form. In this presentation, we will discuss the prerequisites for the drug material itself to be successfully converted into an amorphous form. The criteria amorphization ability, supersaturation propensity and physical stability will be defined and key experiments to address these critical quality attributes will be described.

In the second part of the presentation, we will shift focus from pure drugs to amorphous solid dispersions. The use of amorphous solid dispersions is a commonly applied formulation strategy to improve the oral bioavailability of poorly water-soluble drugs by overcoming dissolution rate and/or solubility limitations. While bioavailability enhancement of amorphous solid dispersions is well documented, it has often been a challenge to establish a predictive model describing in vitro-in vivo correlation (IVIVC). We will discuss formation, solubility advantages and in vivo in vitro relationships of amorphous solid dispersions.