Investigating the effect of supramolecular systems on biopharmaceutical properties of Albendazole desmotropes

GARNERO CLAUDIA; BONGIOANNI AGUSTINA; LONGHI MARCELA

Rosario

Congreso; Cuarta Reunión Internacional de Ciencias Farmacéuticas; 2016

Albendazole (ABZ), a benzimidazole carbamate, is one of the most effective broad-spectrum anthelmintic agents with activity against human and animal parasites. ABZ belongs to biopharmaceutical classification system type II.1 Besides, two solids forms enantiotropically related have been reported and designated as ABZI and ABZII.2 Having in mind the improvement on the bioavailability of ABZ and the selection of a proper desmotrope for its pharmaceutical use, the aim of this study was to analyse the effect of supramolecular systems on solubility and dissolution behaviour of ABZI and ABZII.In order to investigate the influence of supramolecular systems on the biopharmaceutical properties of ABZ desmotropes, binary and ternary systems were studied. Among the available ligands capable of forming supramolecular systems that improve certain properties, were selected maltodextrin (MD) and glutamic acid (GLU). The solubility measurements of ABZ (I and II) and the systems ABZI:MD, ABZII:MD, ABZI:MD:GLU and ABZII:MD:GLU were performed in aqueous and simulated gastric fluid (SGF) without enzymes, according to the method of Higuchi and Connors.3 Solid-state systems in equimolar ratio were prepared by kneading method and physical mixture. These were characterized by powder X-ray diffraction and scanning electron microscopy, and their dissolution behaviors were evaluated.Solubility studies revealed that ABZII is the most soluble form (6 g/mL in water, and 297 g/mL in SGF). Their binary and ternary systems showed the higher solubility in SGF (1.2 mg/mL and 738 g/mL, respectively), however, ABZI systems achieved significant solubility increase. The stability constants calculated for binary systems in SGF were 411 M-1 (ABZI:MD) and 308 M-1 (ABZII:MD). Moreover, the dissolution profiles of ABZII systems displayed the higher increments of drug dissolved (over 80%). Our results revealed that solubility and dissolution of both ABZ forms were significantly increased as result of the formation of binary and ternary systems. In conclusion, these supramolecular structures constitute an alternative tool to improve physicochemical properties of ABZ, with potential application for the preparation of pharmaceutical dosage products.