title: Probing hydrogen bonding in cocrystals and amorphous dispersions using (14)N-(1)H HMQC solid-state NMR.
abstract: Cocrystals and amorphous solid dispersions have generated interest in the pharmaceutical industry as an alternative to more established solid delivery forms. The identification of intermolecular hydrogen bonding interactions in a nicotinamide palmitic acid cocrystal and a 50% w/w acetaminophen-polyvinylpyrrolidone solid dispersion are reported using advanced solid-state magic-angle spinning (MAS) NMR methods. The application of a novel (14)N-(1)H HMQC experiment, where coherence transfer is achieved via through-space couplings, is shown to identify specific hydrogen bonding motifs. Additionally, (1)H isotropic chemical shifts and (14)N electric field gradient (EFG) parameters, both accessible from (14)N-(1)H HMQC experiments, are shown to be sensitive to changes in hydrogen bonding geometry. Numerous indicators of molecular association are accessible from this experiment, including NH cross-peaks occurring from intermolecular hydrogen bonds and changes in proton chemical shifts or electric field gradient parameters. First-principles calculations using the GIPAW approach that yield accurate estimates of isotropic chemical shifts, and EFG parameters were used to assist in assignment. It is envisaged that (14)N-(1)H HMQC solid state NMR experiments could become a valuable screening technique of solid delivery forms in the pharmaceutical industry.
authors.affiliation: Department of Physics, University of Warwick , Coventry CV4 7AL, United Kingdom.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Tatton
authors.forename: Tran N
authors.initials: TN
authors.lastname: Pham
authors.forename: Frederick G
authors.initials: FG
authors.lastname: Vogt
authors.forename: Dinu
authors.initials: D
authors.lastname: Iuga
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Edwards
authors.forename: Steven P
authors.initials: SP
authors.lastname: Brown
mesh_terms: D000082:Acetaminophen / Q000737:chemistry; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D011205:Povidone / Q000737:chemistry
chemical_list: D000082:Acetaminophen; D011205:Povidone