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Molecular Properties of Flurbiprofen and its Solid Dispersions with Eudragit RL100 Studied by High- and Low-Resolution Solid-State Nuclear Magnetic Resonance
Authors:Giulia Mollica  Marco Geppi  Rosario Pignatello  Carlo A Veracini
Institution:(1) Dipartimento di Chimica e Chimica Industriale, Università di Pisa, v. Risorgimento 35, 56126 Pisa, Italy;(2) Dipartimento di Scienze Farmaceutiche, Università degli Studi di Catania, viale A. Doria 6, 95125 Catania, Italy
Abstract:Purpose Investigation of the conformational and molecular dynamic properties of the acidic and sodium salt forms of Flurbiprofen and their solid dispersions with Eudragit? RL100, obtained by two different preparation methods (physical mixtures and coevaporates), and of the mixing degree between the two components in the dispersions.Materials and Methods 1H and 13C high-resolution solid state NMR techniques, including Single Pulse Excitation-MAS, CP-MAS, FSLG-HETCOR; low-resolution 1H FID analysis; 1H spin-lattice relaxation time measurements.Results Conformational, molecular packing and dynamic differences were observed between the two pure forms of flurbiprofen, as well as between the pure drugs and the corresponding coevaporates. In the coevaporates of the two flurbiprofen forms, drug and polymer appear intimately mixed; their chemical interactions were detected and characterized.Conclusions A combined analysis of several 13C and 1H high- and low-resolution solid state NMR experiments allowed the investigation of the conformational 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 compared to the in vitro drug release profiles given by these solid dispersions.
Keywords:coevaporates  conformational properties  cross-polarization magic-angle Spinning (CPMAS)  drug-polymer interactions  FSLG-HETCOR  proton spin diffusion  spin-lattice relaxation times and FID analysis                  1H and 13C chemical shifts
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