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Astemizole/Cyclodextrin Inclusion Complexes: Phase Solubility, Physicochemical Characterization and Molecular Modeling Studies

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Abstract

Guest–host interaction of astemizole (Astm) with cyclodextrins (CDs) has been investigated using phase solubility diagrams (PSD), differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), proton nuclear magnetic resonance (1H-NMR) and molecular mechanical modeling (MM+). Estimates of the complex formation constant, K 11, show that the tendency of Astm to complex with CDs follows the order: β-CD>HP-β-CD>γ-CD, α-CD. 1:1 Astm/β-CD complex formation at pH=5.0 was largely driven by the hydrophobic effect (desolvation), which was quantitatively estimated at −16.5 kJ⋅mol−1, whereas specific interactions contribute only −5.3 kJ⋅mol−1 to 1:1 complex stability (ΔG o11 =−22.7 kJ⋅mol−1). The percentage contributions of the hydrophobic effect and specific interactions were therefore 73 and 27%, respectively. Both enthalpic and entropic factors contribute equally well (−11 kJ⋅mol−1 each) to 1:1 Astm/β-CD complex stability. 1H-NMR and MM+ molecular modeling studies indicate the formation of different isomeric 1:1 and 1:2 complexes. The dominant driving force for complexation is evidently van der Waals with very little electrostatic contribution. PSD, 1H-NMR, DSC, XRPD and MM+ studies proved the formation of inclusion complexes in solution and the solid state.

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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, University of Jordan, Amman, Jordan

    Mohammad B. Zughul

  3. Department of Environmental Science, Lancaster University, Lancaster, UK

    J. Eric D. Davies

Authors
  1. Mahmoud M. Al Omari
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  2. Mohammad B. Zughul
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  3. J. Eric D. Davies
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  4. Adnan A. Badwan
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Correspondence to Mahmoud M. Al Omari.

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Al Omari, M.M., Zughul, M.B., Davies, J.E.D. et al. Astemizole/Cyclodextrin Inclusion Complexes: Phase Solubility, Physicochemical Characterization and Molecular Modeling Studies. J Solution Chem 37, 875–893 (2008). https://doi.org/10.1007/s10953-008-9277-z

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  • DOI: https://doi.org/10.1007/s10953-008-9277-z

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