Inclusion complexes of melatonin with modified cyclodextrins

  • Hideko Maeda
  • Yu Ogawa
  • Hirokazu Nakayama
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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