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Characterization of inclusion complexes of betahistine with β-cyclodextrin and evaluation of their anti-humidity properties

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Abstract

The formation of inclusion complexes between betahistine (BTH) and the β-CD derivatives were investigated. The binding constant (K c ) of the BTH/β-cyclodextrin (β-CD) inclusion complex was determined to be 1400 L/mol based on UV data. The structure of the BTH/β-CD complex in aqueous solution was examined by 1H–1H rotating frame nuclear Overhauser effect spectroscopy (ROESY) NMR, and the pyridine ring and side chain moiety of the BTH molecule were found to be inserted from the secondary hydroxyl face of the β-CD. The thermal properties of the solid BTH/β-CD inclusion complexes prepared by kneading and freeze-drying methods were studied by differential scanning calorimetry, and for comparison, solid betahistine mesilate (BTHm)/β-CD inclusion complexes were similarly prepared. Humidity tests showed that the solid BTH/β-CD complexes exhibited less moisture absorption compared to the BTHm alone and BTHm/β-CD complexes.

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Acknowledgments

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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  1. Department of Functional Molecular Chemistry, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-machi, Higashinada-ku, Kobe, 658-8558, Japan

    Hideko Maeda, Yukiko Iga & Hirokazu Nakayama

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  1. Hideko Maeda
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  2. Yukiko Iga
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  3. Hirokazu Nakayama
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Correspondence to Hideko Maeda.

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Maeda, H., Iga, Y. & Nakayama, H. Characterization of inclusion complexes of betahistine with β-cyclodextrin and evaluation of their anti-humidity properties. J Incl Phenom Macrocycl Chem 86, 337–342 (2016). https://doi.org/10.1007/s10847-016-0658-4

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  • DOI: https://doi.org/10.1007/s10847-016-0658-4

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