Elena V Parfenyuk1, Ekaterina S Dolinina2. 1. Laboratory of Chemistry of Hybrid Nanomaterials and Supramolecular Systems, G.A. Krestov Institute of Solution Chemistry of Russian Academy of Sciences, 1 Akademicheskaya Str., Ivanono, 153045, Russian Federation. 2. Laboratory of Chemistry of Hybrid Nanomaterials and Supramolecular Systems, G.A. Krestov Institute of Solution Chemistry of Russian Academy of Sciences, 1 Akademicheskaya Str., Ivanono, 153045, Russian Federation. terrakott37@mail.ru.
Abstract
PURPOSE: The work is devoted to synthesis and study of warfarin composites with unmodified, methyl and phenyl modified silica in order to develop controlled release formulation of the anticoagulant. METHODS: The composites were prepared by two routes, adsorption and sol-gel, and characterized with FTIR spectroscopy, dynamic light scattering and DSC methods. The drug release behavior from the composites in media with pH 1.6, 6.8 and 7.4 was analyzed in vitro. The release kinetics of the warfarin - silica composites prepared by the two routes was compared among each other and with analogous silica composites with water soluble drug molsidomine. RESULTS: The comparative analysis showed that in general the kinetic regularities and mechanisms of release for both drugs are similar and determined by nonuniform distribution of the drugs over the silica matrixes and stability of the matrixes in the studied media for the adsorbed composites and uniformly distributed drug and more brittle structure for the sol-gel composites. CONCLUSIONS: The sol-gel composite of warfarin - phenyl modified silica is perspective for further development of novel warfarin formulation with controlled release because it releases warfarin according to zero-order kinetic law with approximately equal rate in the media imitating different segments of gastrointestinal tract.
PURPOSE: The work is devoted to synthesis and study of warfarin composites with unmodified, methyl and phenyl modified silica in order to develop controlled release formulation of the anticoagulant. METHODS: The composites were prepared by two routes, adsorption and sol-gel, and characterized with FTIR spectroscopy, dynamic light scattering and DSC methods. The drug release behavior from the composites in media with pH 1.6, 6.8 and 7.4 was analyzed in vitro. The release kinetics of the warfarin - silica composites prepared by the two routes was compared among each other and with analogous silica composites with water soluble drug molsidomine. RESULTS: The comparative analysis showed that in general the kinetic regularities and mechanisms of release for both drugs are similar and determined by nonuniform distribution of the drugs over the silica matrixes and stability of the matrixes in the studied media for the adsorbed composites and uniformly distributed drug and more brittle structure for the sol-gel composites. CONCLUSIONS: The sol-gel composite of warfarin - phenyl modified silica is perspective for further development of novel warfarin formulation with controlled release because it releases warfarin according to zero-order kinetic law with approximately equal rate in the media imitating different segments of gastrointestinal tract.