title: Evidence for solid- and liquid-state interactions in a furosemide-polyvinylpyrrolidone solid dispersion.
abstract: The solid-state interactions between furosemide (FUR) and polyvinylpyrrolidone (PVP) in a solid dispersion system have been investigated by dispersive and Fourier Transform IR. Using spectral subtraction procedures, shifts to lower frequencies are seen in FUR-NH stretching vibrations in amorphous FUR-PVP systems in comparison with the crystalline FUR spectrum. The magnitude of shifts are similar to those seen when FUR is dissolved in the hydrogen-bonding solvent 1,4 dioxan (0.015-0.155 M, 20 degrees C). Spectral assignment indicates the FUR sulfonamide group binds to PVP in preference to the FUR secondary amine which is shown to possess an intramolecular hydrogen bond by analysis of published X-ray crystal data. With a molecular graphics computer program, the FUR crystal unit cell was compiled, and analyses of nonbonded intermolecular distances are useful in interpreting IR shift data in amorphous solid dispersions. A study of FUR-PVP interactions in solution, examined by proton NMR, reveals a downfield shift of the FUR sulfonamide proton resonance. This shift exhibits dilution and temperature (298-338 K) dependence consistent with an intermolecular hydrogen bond. The secondary amine proton resonance exhibits temperature but not dilution or solvent bonding potential dependence, characteristics of an intramolecular hydrogen bond. The proposed hydrogen bond FUR-PVP interaction may account for the formation and stabilization of the amorphous solid dispersion.
authors.affiliation: Postgraduate School of Pharmacy, Bradford University, West Yorks, UK.
authors.forename: C
authors.initials: C
authors.lastname: Doherty
authors.forename: P
authors.initials: P
authors.lastname: York
mesh_terms: D005665:Furosemide / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D011205:Povidone / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D005665:Furosemide; D011205:Povidone