Structural elucidation of rapid solution-mediated phase transitions in pharmaceutical solids using in situ synchrotron SAXS/WAXS

Drug development programs are increasingly progressing poorly water-soluble candidates into formulation and optimization programs, leading to an increased focus on strategies to address limited solubility and compromised dissolution performance for solid state products. Engineering materials containing a more soluble crystalline or amorphous solid form is one approach to address the problem of solubility. However, these metastable forms will revert over time to more stable, less soluble crystalline forms, through a process which is often mediated by contact with a solvent,10 such as fluid in the gastrointestinal tract. Solution-mediated transformations are an important issue in the development of solid state drug formulations, due to the potential for solid state changes during disintegration and dissolution processes of pharmaceutical solids in the gastrointestinal environment, leading to changes in solubility and potentially variable bioavailability. Solutionmediated phase transformations may also cause problems during the processing of the dosage form, or during standard quality control dissolution testing.