17O Solid-State NMR as a Sensitive Probe of Hydrogen Bonding in Crystalline and Amorphous Solid Forms of Diflunisal

O-17 solid-state NMR (SSNMR) can provide insight into hydrogen bonding interactions in pharmaceutical polymorphs, cocrystals, and amorphous dispersions. When combined with straightforward O-17 synthetic labeling, the use of O-17 SSNMR allows for direct study of key interactions such as hydrogen bonding in these systems. In this work, novel applications of O-17 SSNMR are demonstrated in the analysis of a polymorph of diflunisal, a cocrystal of diflunisal with pyrazinamide, and amorphous,dispersions, of diflunisal in two polymers. The observation of O-17 nucleus is shown to be a highly specific and useful alternative More conventional studies the H-1, C-13, and F-19 nuclei in these systems and offers unique insight into hydrogen bonding interactions. Quantum Chemical calculations are used to assess the O-17 SSNMR. measurements. for the polymorph of diflunisal for which a Crystal structure has been previously determined Empirical hydrogen,bonding trends are then examined in:the cocrystal and amorphous solid forms using O-17 NMR parameters. A novel application of H-1-O-17 cross-polarization heteronuclear correlation (CP-HETCOR) experiments is also demonstrated for the cocrystal and two dispersions. This experiment offers specific information about proton environments in proximity to the labeled oxygen Sites. The use of O-17 SSNMR techniques extends the utility of SSNMR in applications to cocrystals and amorphous dispersions.