Inclusion complexes of melatonin with modified cyclodextrins

The solubility of melatonin (MT) was improved with the addition of modified cyclodextrins (CDs). The solubilities of MT in the presence of beta-cyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD), mono-6-O-maltosyl-beta-cyclodextrin (mono-G(2)-beta-CD), methyl-beta-cyclodextrin (Me-beta-CD), and sulfobutylether-beta-cyclodextrin (SBE-beta-CD) were higher than that of MT itself. In particular, the solubility of MT in the presence of SBE-beta-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-beta-CD inclusion complex. The structure of the MT/SBE-beta-CD complex in aqueous solution was examined by H-1-H-1 rotating frame nuclear overhauser effect spectroscopy NMR. A 5-methoxy moiety of MT was included from the secondary hydroxyl face of SBE-beta-CD. The MT/SBE-beta-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.