Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 24, Pages -Publisher
MDPI
DOI: 10.3390/ijms232416119
Keywords
cyclodextrins; inclusion complexes; fluorescence; NMR spectroscopy; solubility isotherms; thermodynamic parameters
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This study investigated the complexation of GEM with β-CD and its derivatives under different conditions. Stable constants were determined using multiple techniques, and the advantages and drawbacks of each analytical technique were discussed. Additionally, the thermodynamic parameters of complexation were studied, and the complexation of solid dispersions was evaluated using X-ray diffraction.
Gemfibrozil (GEM) is a hypolipidemic agent, which is effective in reducing serum cholesterol and triglyceride levels. Complexation of GEM with native beta-cyclodextrin (beta-CD) and with the derivatives hydroxypropyl-beta- and randomly methylated beta-CD (HP beta-CD and Me beta-CD) was studied in aqueous solution of pH 2.8 and 7.0. The stability constants were determined by spectrofluorimetry, H-1-NMR spectroscopy and solubility assays. Considering the well-known difficulties to obtain similar stability constants by different techniques, the agreement of the values obtained supports the reliability of the results presented. The advantages and drawbacks of each analytical technique for the study of inclusion complexation were discussed as well. In addition, the thermodynamic parameters of complexation, enthalpy (Delta H) and entropy (Delta S), were determined and related to the type of molecular interactions that take place between GEM and the different cyclodextrins. Finally, solid dispersions were prepared by co-evaporation, kneading, vacuum desiccation, and coprecipitation, and complexation was evaluated by X-ray diffraction.
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