Inclusion complexes of melatonin with modified cyclodextrins
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The solubility of melatonin (MT) was improved with the addition of modified cyclodextrins (CDs). The solubilities of MT in the presence of β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), mono-6-O-maltosyl-β-cyclodextrin (mono-G2-β-CD), methyl-β-cyclodextrin (Me-β-CD), and sulfobutylether-β-cyclodextrin (SBE-β-CD) were higher than that of MT itself. In particular, the solubility of MT in the presence of SBE-β-CD was 11 times higher than that of MT itself. The stability constant (K) obtained based on the fluorescence intensity was 490 L/mol for the MT/SBE-β-CD inclusion complex. The structure of the MT/SBE-β-CD complex in aqueous solution was examined by 1H–1H rotating frame nuclear overhauser effect spectroscopy NMR. A 5-methoxy moiety of MT was included from the secondary hydroxyl face of SBE-β-CD. The MT/SBE-β-CD inclusion complex was prepared by the freeze-drying method. The results of X-ray diffraction and differential scanning calorimetry confirmed the formation of the complex in solid.
KeywordsMelatonin Sulfobutylether-β-cyclodextrin Inclusion complexes Solubility
The authors thank Assistant Professor C. Tode of Kobe Pharmaceutical University for the measurements of 1H–1H COSY and 1H–1H ROESY NMR spectra.
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