Related Experiment Video
Updated: May 24, 2025

Application and Methodology of the Non-destructive 19F Time-domain NMR Technique to Measure the Content in Fluorine-containing Drug Products
Published on: August 22, 2017
Probing the Effect of Fluorine on Hydrogen Bonding Interactions in a Pharmaceutical Hydrate Using Advanced
Chaithanya Hareendran1,2, T G Ajithkumar1,2
1Central NMR Facility and Physical/Materials Chemistry Division, CSIR-National Chemical Laboratory, Pune 411008, India.
None:
Structural studies of pharmaceutical hydrates are essential to understanding stability-related issues, especially during the heating process of formulation. A thorough understanding of the hydration and dehydration behavior of active pharmaceutical ingredient (API) hydrate is also important since phase transitions can occur during the formulation process. This is because dehydration could result in a considerable rearrangement in the structure if water-API hydrogen bonding is present. We perform advanced solid-state NMR experiments on regorafenib monohydrate to investigate the role of fluorine in hydrogen bonding interaction, and the results are compared to its anhydrous form and its structural analogue, namely, sorafenib. Our results show that significant structural changes could not be observed on dehydration. Based on our study, it can be concluded that the introduction of fluorine restricts the intramolecular hydrogen bonding and the asymmetry in the structure of regorafenib monohydrate is absent, in comparison to sorafenib.
Related Concept Videos
Hydrogen Bonds
Other Nuclides: 31P, 19F, 15N NMR
While fluorine-19 and phosphorous-31 have high natural abundances (100%) and positive gyromagnetic ratios, nitrogen-15 has a low natural abundance and a negative gyromagnetic ratio. However, nitrogen-15 is still preferred over nitrogen-14 (which has a...
Molecular Shape and Polarity
Intermolecular Forces
Hybridization of Atomic Orbitals I
Valence Bond Theory

