(30a) Towards a Better Understanding of Amorphous Solids and Supercooled Liquids and Their Stability During Pharmaceutical Development

A very high percentage of drug candidates in development are insoluble. These compounds often have low bioavailability due to solubility or dissolution limited absorption. Nonconventional formulations based on amorphous solids prepared by spray drying or hot melt extrusion can often provide improved exposure over conventional formulations based on crystalline material, and have been applied widely. Therefore, a good understanding of amorphous solids and being able to predict their physical stability are very important.

The present study attempts to identify the key thermodynamic and dynamic properties of amorphous solids that may be used to predict or correlate with their stability. This presentation will focus on the dynamic properties and show results from the study on relaxation of amorphous solids and supercooled liquids for several drug compounds. Enthalpy relaxation was measured with differential scanning calorimetry (DSC) for amorphous solids and dielectric relaxation was investigated for supercooled liquids. Our results suggested that these two relaxation processes are correlated and knowledge obtained from the dynamics of a supercooled liquid provides useful information on its corresponding amorphous phase. The effect of polymer additives, amorphous preparation method, and salt formation on the dynamics of amorphous solids will also be discussed.