Formulation and Quality – Chemical
2019 PharmSci 360
The complexity of modern therapeutic modalities and amorphous solid dispersions challenges solid-state analysis and pushes the boundary for investigating physiochemical properties at a higher resolution. Microscopic properties, including molecular interaction, miscibility, and homogeneity in solid dosages, play fundamental roles in manipulating stability, processability, and bioavailability, and are often optimized via chemical, physical, and mechanical strategies. Investigation of molecular behaviors enables a mechanistic understanding of critical pharmaceutical attributes and facilitate the design of formulation composition and manufacturing processes. This presentation will provide advanced solid-state NMR spectroscopic techniques, for the first time, to probe the intermolecular interaction of amorphous drug substances and polymeric additives at angstrom (Å) level. Specifically, we will introduce a novel technique, spin diffusion NMR (SD-NMR), for quantifying drug-polymer miscibility and homogeneity in pharmaceutical dispersions at sub-100 nm resolution.