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

The complexation of NSAIDs (nonsteroidal antiinflamatory drugs): Ibuprofen (Ibu), Ketoprofen (Ket) and Naproxen (Nap) with beta cyclodextrin (beta CD) has been studied from structural and thermodynamic points of view. The binding constants of NSAIDs-beta CD 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 a parts per thousand CENap < CEKet. Experimental measurements indicated that KNap-beta CD > KIbu-beta CD > KKet-beta CD, and that the apparent stability constants decrease as the polarity of the solvent decreases. The changes of a dagger HA(0) (enthalpy), a dagger SA(0) (entropy) and a dagger GA(0) (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 (a dagger HA(0)A < 0), entropy was found unfavorable (a dagger SA(0)A < 0) and Gibbs free energy was favorable (a dagger GA(0)A < 0). The theoretical results are in agreement with the experimental parameters associated with the encapsulation process.