Prediction of physical and chemical stability

Solid dispersion formulations are amorphous materials, and therefore require special attention to ensure long-term stability at desired storage conditions. Agere’s Stability Prediction technology combines rapid measurement of crystallinity and/or chemical degradation with computational methods to predict long-term shelf stability. The methodology using standard and custom methods for measuring the state of the drug (for example, degree of crystallinity) in the formulation at accelerated temperature and humidity conditions and uses this data in physical models to predict stability. Generally, a complete stability map as shown below can be generated with a few grams of material in as little as a few weeks. Longer term studies are then completed to confirm the early predictions.

Computational Tools

Mathematical tools are based on determining the rate at which drug in a solid dispersion formulation crystallizes or degrades at a range of temperature and humidity conditions. These data are fit to a modified Arrhenius function which enables the determination of the water-dependent rate constants. A set of these constants is then used in a mathematical algorithm to obtain predictions at any temperature, time, and storage humidity.