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Updated: Apr 25, 2026

Synthesis of Cyclic Polymers and Characterization of Their Diffusive Motion in the Melt State at the Single Molecule Level
Published on: September 26, 2016
Understanding API-polymer proximities in amorphous stabilized composite drug products using fluorine-carbon 2D HETCOR
1Drug Product Science and Technology, Material Science Division, Bristol-Myers Squibb , New Brunswick, New Jersey 08903, United States.
Abstract:
A simple and robust method for obtaining fluorine-carbon proximities was established using a (19)F-(13)C heteronuclear correlation (HETCOR) two-dimensional (2D) solid-state nuclear magnetic resonance (ssNMR) experiment under magic-angle spinning (MAS). The method was applied to study a crystalline active pharmaceutical ingredient (API), avagacestat, containing two types of fluorine atoms and its API-polymer composite drug product. These results provide insight into the molecular structure, aid with assigning the carbon resonances, and probe API-polymer proximities in amorphous spray dried dispersions (SDD). This method has an advantage over the commonly used (1)H-(13)C HETCOR because of the large chemical shift dispersion in the fluorine dimension. In the present study, fluorine-carbon distances up to 8 Å were probed, giving insight into the API structure, crystal packing, and assignments. Most importantly, the study demonstrates a method for probing an intimate molecular level contact between an amorphous API and a polymer in an SDD, giving insights into molecular association and understanding of the role of the polymer in API stability (such as recrystallization, degradation, etc.) in such novel composite drug products.
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