Crystallization kinetics in amorphous solid dispersions can be quantified by water sorption measurements

INTRODUCTION

Most new active pharmaceutical ingredients (APIs) exhibit a very low solubility in water, leading to an insufficient absorption in the gastrointestinal tract and thus poor bioavailability. Several approaches exist to increase the bioavailability of APIs. A promising approach is to transform the -usually crystalline- API into its amorphous form, which is better water soluble, but also metastable against crystallization.

The most common stabilizing strategy is to embed the amorphous API in a polymer matrix resulting in a so-called amorphous solid dispersion (ASD). However, as the API loading usually exceeds its solubility in the polymer, the API tends to recrystallize during storage. This is particularly true for humid storage conditions as the ASDs may absorb remarkable amounts of water which drastically decrease the solubility of the hydrophobic API in the ASD. Moreover, absorbed water also lowers the ASD glass-transition temperature thus decreasing both, the thermodynamic as well as the kinetic stability of ASDs.