CONICET | Buscador de Institutos y Recursos Humanos

Albendazole (ABZ), a benzimidazole carbamate, is an anthelmintic compound widely used in the treatment of systemic nematode infections. Nevertheless, its effectiveness is limited by its poor water solubility (1 μg/mL at 25 °C) and the consequent poor bioavailability, producing an unpredictable therapeutic response. Several strategies may be employed to increase solubility, dissolution rate and oral bioavailability of poorly water soluble drugs, including the formulation of cyclodextrin (CD) inclusion complexes. CD derivatives presenting acidic groups in their structure may interact strongly with basic drugs modifying the inclusion complexes stability. Therefore, the aim of this work was focused in the synthesis of a succinyl-β-CD (S-β-CD) derivative to design oral delivery systems and to improve the solubility and dissolution rate of ABZ. Initially, the syntheses of S-β-CD derivative was carried out according to similar methodology previously reported by Garcia et al. The characterization of β-CD derivative was performed by carboxylic titration, mass spectrometry, infrared spectroscopy and nuclear magnetic resonance. The interaction between ABZ and S-β-CD was evaluated by phase solubility analysis, nuclear magnetic resonance and mass spectrometry. Additionally, solid systems were studied comparing the techniques: physical mixture and spray dried. The results obtained from the phase solubility analysis and mass spectrometry, verified that the complexes were formed in a 1:1 molar ratio. The characterization studies confirmed the drug inclusion complex in the solid state. The proposed system allowed to increase significantly the ABZ solubility and the dissolution rate values in comparison to the pure drug and the complex prepared by ABZ:β-CD. Keywords: cyclodextrin derivatives, dissolution rate, nuclear magnetic resonance.