Effect of β-cyclodextrins based nanosponges on the solubility of lipophilic pharmacological active substances (repaglinide)
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Cyclodextrin based nanosponges (CD-NS) are nanostructured cross-linked polymers, usually obtained by reacting cyclodextrin with a cross-linker such as carbonyldiimidazole, organic carbonates or (±) epichlorohydrin. They have been used to increase the solubility and stability of poorly soluble pharmacological active substances, as they combine the complex forming properties of CDs and properties of polymers (such as the high molecular weight). The affinity of CDs for certain lipophilic molecules is characteristic to the polymeric nano-structured system and allows the development of specific drug delivery systems. Knowing that cyclodextrin capacity to form inclusion complexes is maintained and enhanced when the CD molecules form aggregates, cross-link together or copolymerize with other compounds, we have synthesized cyclodextrin based nanosponges (from β-cyclodextrin and sulfobutylether-β-cyclodextrin). The complexing properties of the polymers were investigated against repaglinide (a hypoglycemic agent, practically insoluble in water). Solubility studies were performed according to the method reported by Higuchi and Connors and the phase solubility diagrams were plotted. The repaglinide-nanosponges complexes were prepared, lyophilized and the resulted inclusion complexes were characterized by FT-IR and NMR. The solubility profile and the loading capacity of the cyclodextrin based polymers were also determined.
KeywordsNanosponge Repaglinide β-Cyclodextrin Sulfobutylether-β-cyclodextrin Solubility
We thank Dr. Mihai Nitulescu for the help with the FTIR–ATR spectra.
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