Molecular Encapsulation of Flurbiprophen and/or Ibuprophen by Hydroxypropyl-β-cyclodextrin in Aqueous Solution. Potentiometric and Molecular Modeling Studies

Abstract

Thermodynamic and structural studies of the binding of the nonsteroidal antiinflammatory drugs, flurbiprophen and ibuprophen, to hydroxypropyl-β-cyclodextrin (HPBCD) have been carried out from pH potentiometric measurements, molecular mechanics, and dynamics calculations. The potentiometric study was performed by measuring the pH of aqueous solutions of the drugs as a function of cyclodextrin concentration, at several temperatures ranging from 15 to 40 °C. The dissociation constants of the drugs, as well as the binding constants of the inclusion complexes formed by HPBCD and the ionized and nonionized drugs, have been simultaneously determined at all the temperatures. The nonionic forms have shown a higher affinity to HPBCD than their ionic counterparts. A van't Hoff analysis of the determined binding constants reveals that the complexes formed by the flurbiprophen species and HPBCD are enthalpy driven, with a favorable enthalpic term and an unfavorable entropic term. Both contributions are found to be te...