UNITEFA   23945
UNIDAD DE INVESTIGACION Y DESARROLLO EN TECNOLOGIA FARMACEUTICA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Characterization of the inclusion complex formed by the antihelmintic drug Mebendazole and β-cyclodextrin. Molecular modeling and FT-IR analysis
Autor/es:
E. SAIDMAN; L. ARAGON; M. SANCHO; M. LONGHI
Lugar:
Cordoba
Reunión:
Congreso; 3a Reunión Internacional de Ciencias Farmacéuticas; 2014
Institución organizadora:
Universidad Nacional de Córdoba
Resumen:
Mebendazole (MBZ) is commonly used as a broad spectrum antihelmintic drug, commercialized as a tablet formulation or as a suspension. However, this drug is associated with a low aqueous solubility and therefore, a poor absorption from the intestinal tract. Different methods can be used to increase the aqueous solubility of a drug, being the formation of inclusion complexes with cyclodextrins one of the most employed. A molecular modeling analysis and FT-IR spectroscopy measurements were performed in order to elucidate the intermolecular interactions between MBZ and -cyclodextrin (CD). The inclusion process between neutral and protonated MBZ (MBZ-H+) with CD was simulated with the PM3 semiempirical method, and two possible orientations were considered for each complex, Head up and Head Down, following a previously published report [1]. The more stable complexes were further optimized with a two-layer ONIOM (B3LYP/6-31G(d):PM3) method and the interactions between the guest drug and CD were quantified with a NBO population analysis. The FT-IR spectra of MBZ, CD, the inclusion complex obtained by freeze dried and the physical mixture were registered in a IRAffinity-1 Shimadzu spectrophotometer, with a spectral resolution of 4 cm-1. The PM3 and ONIOM calculations indicated that the Head Down orientation is the preferred one for MBZ and MBZ-H+ inclusion complexes, by 5 and 9 kJ/mol, respectively. The benzimidazolic moiety is completely embedded in the CD cavity in both cases. The NBO results showed an intermolecular H-bond between the imidazolic N of MBZ and one OH group from CD, with a bond length of 2.61 Å and with a stabilization energy of 7.9 kJ/mol. This interaction was further confirmed by FT-IR spectroscopy, where the MBZ stretching C=N band is located at 1645 cm-1 in the free drug and at 1653 cm-1 in the freeze dried MBZ:CD complex.