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Comparative Study of the Inclusion Complexation of Pizotifen and Ketotifen with Native and Modified Cyclodextrins

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Abstract

The interaction of two benzocycloheptanes namely, pizotifen (Pizo) and ketotifen (Keto), with cyclodextrins (CDs: α-, β-, γ-, and HP-β-CDs) has been investigated by several techniques including phase solubility, X-ray powder diffractometry, 1H-nuclear magnetic resonance and molecular mechanical modeling. The effects of CD type, pH, ionic strength and temperature on complex stability were also explored. The complex formation constant (K 11) values for the Pizo/CD system follows the decreasing order β-CD > γ-CD > HP-β-CD > α-CD. However, for the Keto/CD system it follows the decreasing order γ-CD > β-CD > HP-β-CD > α-CD. The tendency of Pizo and Keto to complex with β-CD is driven to the extent of 70% by the hydrophobic effect. Complex formation of Keto and Pizo was substantially driven by entropy (>100 J⋅mol−1⋅K−1) but slightly retarded by enthalpy (3–8 kJ⋅mol−1). 1H-NMR and MM+ studies indicate multimodal inclusion of the methylpiperadine, thiophene and phenyl moieties into the β-CD cavity.

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Authors and Affiliations

  1. The Jordanian Pharmaceutical Manufacturing Company, Naor, Jordan

    Mahmoud M. Al Omari & Adnan A. Badwan

  2. Department of Chemistry, The Hashemite University, Zarqa, Jordan

    Musa I. El-Barghouthi

  3. Department of Chemistry, University of Jordan, Amman, Jordan

    Mohammad B. Zughul

  4. Department of Environmental Science, Lancaster University, Lancaster, England, UK

    J. Eric D. Davies

Authors
  1. Mahmoud M. Al Omari
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  2. Musa I. El-Barghouthi
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  3. Mohammad B. Zughul
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  4. J. Eric D. Davies
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  5. Adnan A. Badwan
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Correspondence to Mahmoud M. Al Omari.

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Al Omari, M.M., El-Barghouthi, M.I., Zughul, M.B. et al. Comparative Study of the Inclusion Complexation of Pizotifen and Ketotifen with Native and Modified Cyclodextrins. J Solution Chem 37, 249–264 (2008). https://doi.org/10.1007/s10953-007-9234-2

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  • DOI: https://doi.org/10.1007/s10953-007-9234-2

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