Review: Use of Thermal, Diffraction, and Vibrational Analytical Methods to Determine Mechanisms of Solid Dispersion Stability

摘要

Formulations such as amorphous dispersions have been proposed to counter the ever present need to make drug products sufficiently soluble. However, a major concern with amorphous pharmaceuticals is physical instability, where the higher free-energy form will spontaneously revert to the more stable (and less soluble) crystalline form. Proposed mechanisms of amorphous pharmaceutical stabilization via solid dispersions are presented, as well as the analytical methods used to understand or monitor physical stability. This work focuses on differential scanning calorimetry, Raman and infrared spectroscopy, and powder X-ray diffraction, based on the general accessibility of these methods and abundant references in the pharmaceutical literature.