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Journal of Solution Chemistry

, Volume 37, Issue 6, pp 875–893 | Cite as

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

  • Mahmoud M. Al Omari
  • Mohammad B. Zughul
  • J. Eric D. Davies
  • Adnan A. Badwan
Article

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 11 o =−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.

Keywords

Astemizole Cyclodextrin Inclusion complexation 1H-NMR Molecular modeling Phase solubility Solvation Hydrophobic effect Thermodynamics 

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Mahmoud M. Al Omari
    • 1
  • Mohammad B. Zughul
    • 2
  • J. Eric D. Davies
    • 3
  • Adnan A. Badwan
    • 1
  1. 1.The Jordanian Pharmaceutical Manufacturing CompanyNaorJordan
  2. 2.Department of ChemistryUniversity of JordanAmmanJordan
  3. 3.Department of Environmental ScienceLancaster UniversityLancasterUK

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