Effect of Buffer Species on the Complexation of Basic Drug Terfenadine
with β-Cyclodextrin |
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Authors: | Mahmoud M Al Omari Mohammad B Zughul J Eric D Davies Adnan A Badwan |
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Institution: | (1) The Jordanian Pharmaceutical Manufacturing Company, Naor, Jordan;(2) Department of Chemistry, University of Jordan, Amman, Jordan;(3) Department of Environmental Science, Lancaster University, Lancaster, England |
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Abstract: | The complexation of terfenadine (Terf) with β-cyclodextrin (β-CD) in solution and solid state has been investigated by phase solubility diagram (PSD), differential scanning calorimetry
(DSC), powder X-ray diffractometry (PXD) and proton nuclear magnetic resonance (1H-NMR). The PSD results indicated that the salt saturation with the buffer counter ion (citrate−2, H2PO4−1 and Cl−1 ions) of Terf (pK
a = 9.5) and the hydrophobic effect play in tandem to increase the value of the complex formation constant (K11) measured at different conditions of pH, ionic strength, buffer type and buffer concentration. The correlation of the free
energy of complex formation (ΔG11) with the free energy of inherent solubility of Terf (ΔGSo) obtained by changing the pH, ionic strength and buffer concentration was used to measure the contribution of the hydrophobic
effect (desolvation) to complex formation. The hydrophobic effect was found to constitute 57.8% of the driving force for complex
stability, while other factors including specific interactions contribute −13.4 kJ/mol. 1H-NMR spectra of Terf–citrate and Terf–HCl salts gave identical chemical shift displacements (ΔΔ) upon complexation, thus
indicating that the counter anions are positioned somewhere outside of the β-CD cavity. DSC, XRPD and 1H-NMR proved the formation of solid Terf/acid/β-CD ternary complexes. |
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Keywords: | β -cyclodextrin buffer type hydrophobic effect multicomponent complexes terfenadine |
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