Determination of apparent binding constants by NSAIDs-βcyclodextrin complexes: HPLC, phase solubility diagrams and theoretical studies

Abstract

The complexation of NSAIDs (nonsteroidal antiinflamatory drugs): Ibuprofen (Ibu), Ketoprofen (Ket) and Naproxen (Nap) with βcyclodextrin (βCD) has been studied from structural and thermodynamic points of view. The binding constants of NSAIDs-βCD complexes were determined by reversed phase liquid chromatography (RP-HPLC) and phase solubility diagrams using a UV–Vis spectrophotometric method varying the working temperature. The complexation efficiency (CE) values were determined: CEIbu ≈ CENap KIbu-βCD > KKet-βCD, and that the apparent stability constants decrease as the polarity of the solvent decreases. The changes of ∆Ho (enthalpy), ∆So (entropy) and ∆Go (Gibbs free energy) for the inclusion process were obtained by means of the van’t Hoff equation. In addition, semiempirical quantum mechanics calculations using the PM6 method were performed. The energetically favorable structures of the inclusion complexes were identified: the most favorable orientation was found to be the head down for all the complexes. Enthalpy for complexation processes was found to be favorable (∆Ho < 0), entropy was found unfavorable (∆So < 0) and Gibbs free energy was favorable (∆Go < 0). The theoretical results are in agreement with the experimental parameters associated with the encapsulation process.