Inclusion complexes of melatonin with modified cyclodextrins

Original Article


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.


Melatonin 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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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of Functional Molecular ChemistryKobe Pharmaceutical UniversityKobeJapan

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