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.
- 1.Poeggeler, B., Saarela, S., Reiter, R.J., Tan, D.-X., Chen, L.-D., Manchester, L.C., Barlow-Walden, L.R.: Melatonin—a highly potent endogenous radical scavenger and electron donor: new aspects of the oxidation chemistry of this indole accessed in vitro. Ann. N. Y. Acad. Sci. 738, 419–420 (1994)CrossRefGoogle Scholar
- 5.Carrillo-Vico, A., Lardone, P.J., Fernández-Santos, J.M., Martín-Lacave, I., Calvo, J.R., Karasek, M., Guerrero, J.M.: Human lymphocyte-synthesized melatonin is involved in the regulation of the interleukin-2/interleukin-2 receptor system. J. Clin. Endocrinol. Metab. 90, 992–1000 (2004)CrossRefGoogle Scholar
- 8.Uekama, K.: Pharmaceutical applications of methylated cyclodextrins. Pharm. Int. 6, 61–65 (1985)Google Scholar
- 9.Brewster, M.E., Estes, K.S., Loftsson, T., Perchalski, R., Derendorf, H., Mullersman, G., Bodor, N.: Improved delivery through biological membranes XXXI : solubilization and stabilization of an estradiol chemical delivery system by modified β-cyclodextrins. J. Pharm. Sci. 77, 981–985 (1988)CrossRefGoogle Scholar
- 15.Higuchi, T., Connors, K.A.: Phase-solubility techniques. Adv. Anal. Chem. Instrum. 4, 117–212 (1965)Google Scholar
- 16.Job, P.: Formation and stability of inorganic complexes in solution. Ann. Chem. 9, 113–203 (1928)Google Scholar