title: Hydrogen Bonding Interactions in Amorphous Indomethacin and Its Amorphous Solid Dispersions with Poly(vinylpyrrolidone) and Poly(vinylpyrrolidone-co-vinyl acetate) Studied Using (13)C Solid-State NMR.
abstract: Hydrogen bonding interactions in amorphous indomethacin and amorphous solid dispersions of indomethacin with poly(vinylpyrrolidone), or PVP, and poly(vinylpyrrolidone-co-vinyl acetate), or PVP/VA, were investigated quantitatively using solid-state NMR spectroscopy. Indomethacin that was (13)C isotopically labeled at the carboxylic acid carbon was used to selectively analyze the carbonyl region of the spectrum. Deconvolution of the carboxylic acid carbon peak revealed that 59% of amorphous indomethacin molecules were hydrogen bonded through carboxylic acid cyclic dimers, 15% were in disordered carboxylic acid chains, 19% were hydrogen bonded through carboxylic acid and amide interactions, and the remaining 7% were free of hydrogen bonds. The standard dimerization enthalpy and entropy of amorphous indomethacin were estimated to be -38 kJ/mol and -91 J/(mol · K), respectively, using polystyrene as the "solvent". Polymers such as PVP and PVP/VA disrupted indomethacin self-interactions and formed hydrogen bonds with the drug. The carboxylic acid dimers were almost completely disrupted with 50% (wt) of PVP or PVP/VA. The fraction of disordered carboxylic acid chains also decreased as the polymer content increased. The solid-state NMR results were compared with molecular dynamics (MD) simulations from the literature. The present work highlights the potential of (13)C solid-state NMR to detect and quantify various hydrogen bonded species in amorphous solid dispersions as well as to serve as an experimental validation of MD simulations.
authors.affiliation: College of Pharmacy, University of Kentucky , 789 South Limestone Street, Lexington, Kentucky 40536, United States.
authors.forename: Xiaoda
authors.initials: X
authors.lastname: Yuan
authors.affiliation: College of Pharmacy, University of Kentucky , 789 South Limestone Street, Lexington, Kentucky 40536, United States.
authors.forename: Tian-Xiang
authors.initials: TX
authors.lastname: Xiang
authors.affiliation: College of Pharmacy, University of Kentucky , 789 South Limestone Street, Lexington, Kentucky 40536, United States.
authors.forename: Bradley D
authors.initials: BD
authors.lastname: Anderson
authors.affiliation: College of Pharmacy, University of Kentucky , 789 South Limestone Street, Lexington, Kentucky 40536, United States.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Munson
mesh_terms: D000577:Amides / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry; D006860:Hydrogen Bonding; D007213:Indomethacin / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods; D056004:Molecular Dynamics Simulation; D011145:Polyvinyls / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D014753:Vinyl Compounds / Q000737:chemistry*
chemical_list: D000577:Amides; D002264:Carboxylic Acids; D011145:Polyvinyls; D011759:Pyrrolidines; D012997:Solvents; D014753:Vinyl Compounds; C505150:poly(N-vinylpyrrolidine); C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D002244:Carbon; C011566:vinyl acetate; D007213:Indomethacin
keywords: PVP; PVP/VA; amorphous; hydrogen bond; indomethacin; solid dispersion; solid-state NMR