PURPOSE: The aim of this study was to investigate, at a molecular level, the structural and dynamic properties of the acidic and sodium salt forms of ibuprofen and their solid dispersions with Eudragit RL100, obtained by two different preparation methods (physical mixtures and co-evaporates), which may affect the release properties of these drugs in their dispersed forms. METHODS: (1)H and (13)C high-resolution solid-state nuclear magnetic resonance techniques, including single-pulse excitation magic-angle spinning, cross-polarization magic-angle spinning, and other selective 1D spectra, as well as more advanced 2D techniques Frequency Switched Lee-Goldburg HETeronuclear CORrelation (FSLG-HETCOR) and Magic Angle Spinning -J- Heteronuclear Multiple-Quantum Coherence (MAS-J-HMQC) and relaxation time measurements were used. RESULTS: A full assignment of (13)C resonances and precise (1)H chemical shift values were achieved for the first time for the two forms of ibuprofen that showed very different inter-conformational dynamic behavior; drug-polymer interactions were observed and characterized in the co-evaporates of the two forms but were much stronger for the acidic form. CONCLUSIONS: A combined analysis of several high-resolution solid-state nuclear magnetic resonance experiments allowed the investigation of the structural and dynamic properties of the pure drugs and of the solid dispersions with the polymer, as well as of the degree of mixing between drug and polymer and of the chemical nature of their interaction. Such information could be related to the in vitro drug release profiles observed for the tested co-evaporates.
PURPOSE: The aim of this study was to investigate, at a molecular level, the structural and dynamic properties of the acidic and sodium salt forms of ibuprofen and their solid dispersions with Eudragit RL100, obtained by two different preparation methods (physical mixtures and co-evaporates), which may affect the release properties of these drugs in their dispersed forms. METHODS: (1)H and (13)C high-resolution solid-state nuclear magnetic resonance techniques, including single-pulse excitation magic-angle spinning, cross-polarization magic-angle spinning, and other selective 1D spectra, as well as more advanced 2D techniques Frequency Switched Lee-Goldburg HETeronuclear CORrelation (FSLG-HETCOR) and Magic Angle Spinning -J- Heteronuclear Multiple-Quantum Coherence (MAS-J-HMQC) and relaxation time measurements were used. RESULTS: A full assignment of (13)C resonances and precise (1)H chemical shift values were achieved for the first time for the two forms of ibuprofen that showed very different inter-conformational dynamic behavior; drug-polymer interactions were observed and characterized in the co-evaporates of the two forms but were much stronger for the acidic form. CONCLUSIONS: A combined analysis of several high-resolution solid-state nuclear magnetic resonance experiments allowed the investigation of the structural and dynamic properties of the pure drugs and of the solid dispersions with the polymer, as well as of the degree of mixing between drug and polymer and of the chemical nature of their interaction. Such information could be related to the in vitro drug release profiles observed for the tested co-evaporates.
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