Interactions of poly(vinylpyrrolidone) with ibuprofen and naproxen: experimental and modeling studies.
OBJECTIVE
To elucidate the differences in the interaction of chiralic ibuprofen (IBP) and naproxen (NAP) with poly(vinylpyrrolidone) (PVP) in a solid state.


METHODS
Drugs/PVP physical mixtures and solid dispersions were characterized by scanning electron microscope (SEM), Fourier transform infrared spectrometry (FT-IR), solid state (13)C NMR spectroscopy, and x-ray diffractometry. Molecular modeling study of the crystal structures and PVP was performed.


RESULTS
A spontaneous conversion of IBP/PVP physical mixtures in a stable glasslike form (solid dispersion) was observed after storage. The enantiomer reacted more strongly than the racemate. NAP did not interact with PVP. The crystal structures of drugs showed differences in the hydrogen bonding, aromatic interactions, molecular energies, and distances inside the crystals. The trimer structure of PVP was built and optimized. It was proposed that each PVP monomer could interact with one IBP dimmer in contrast to NAP, where two out of three PVP monomers faced the catemer carboxylic groups.


CONCLUSIONS
The differences in the interaction of PVP with racemic IBP, enantiomer IBP, and NAP can be related to the differences in their crystal structures. The correlation between the experimental data and the results of the molecular modeling analysis suggest that the IBP dimmer structures are likely to perform HB and aromatic interactions with PVP.
Bogdanova
Svetla
S
Faculty of Pharmacy, Medical University, Sofia, Bulgaria. sbogdanova@pharmfac.acad.bg
Pajeva
Ilza
I
Nikolova
Petya
P
Tsakovska
Ivanka
I
Müller
Bernd
B
D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004347:Drug Interactions; D007052:Ibuprofen / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008855:Microscopy, Electron, Scanning / Q000379:methods; D008958:Models, Molecular; D009288:Naproxen / Q000494:pharmacology*; D011205:Povidone / Q000494:pharmacology*; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013237:Stereoisomerism; D013678:Technology, Pharmaceutical / Q000379:methods; D014961:X-Ray Diffraction / Q000379:methods
D009288:Naproxen; D011205:Povidone; D007052:Ibuprofen