Characterizing Pharmaceutical Formulations Using Solid-State NMR Spectroscopy
Advanced analytical techniques can provide unique insight into the composition and properties of pharmaceutical formulations. In particular, both structural and mobility information can be obtained about the formulations, but the challenge is to relate that information to functional properties such as physical and chemical stability, dissolution rate, and processing parameters. Solid-state NMR spectroscopy is a powerful technique to study polymorphism, form changes upon processing, the presence of small amounts of amorphous drug in crystalline solids (for chemical/physical stability), and small amounts of crystalline drug in amorphous solid dispersions (for physical stability). Solid-state NMR relaxation times have been used to measure particle size, crystal defects, and chemical impurities in crystalline materials. In addition, relaxation times have been used to determine the phase separation of amorphous formulations. Finally, mobility, phase separation, and microenvironment acidity has been studied to predict stability in large-molecule formulations.