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

M. A. FILIPPA; M. I. SANCHO; E. I. GASULL

JOURNAL OF INCLUSION PHENOMENA AND MACROCYCLIC CHEMISTRY

SPRINGER

Lugar: Berlin; Año: 2013 vol. 77 p. 223 - 230

0923-0750

The complexation of NSAIDs (nonsteroidal antiinflamatory drugs): Ibuprofen (Ibu), Ketoprofen (Ket) and Naproxen (Nap) with bcyclodextrin (BCD) has been studied from structural and thermodynamic points of view. The binding constants of NSAIDs-bCD 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 <CEKet. Experimental measurements indicated that KNap-bCD > KIbu-bCD >KKet-bCD, and that the apparent stability constants decrease as the polarity of the solvent decreases. The changes of DH°(enthalpy), DS° (entropy) and DG° (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 (DH°<0), entropy was found unfavorable (DS°<0) and Gibbs free energy was favorable (DG°<0). The theoretical results are in agreement with the experimental parameters associated with the encapsulation process.