Modulated dissolution rate from the inclusion complex of antichagasic benznidazole and cyclodextrin using hydrophilic polymer

Abstract

Benznidazole (BNZ) is the primary chemotherapeutic agent for treating Chagas’ disease; however, its poor water solubility and irregular oral absorption lead to the treatment failure in the chronic phase. The aim of this work was to investigate the utility of the polymer hydroxypropyl methylcellulose (HPMC) in controlling the release of BNZ from solid inclusion complexes with cyclodextrin to overcome the problem of its bioavailability. Preliminary studies of solubility were conducted in solution using selected β-cyclodextrin derivatives according to an experimental mixture design. The best cyclodextrin composition was used to produce solid-state systems by kneading in the presence or absence of HPMC. The formulations were characterized by different physico-chemical techniques, including the dissolution rate. Hydroxypropyl-β-cyclodextrin (HPβCD) produced the greatest improvement in drug solubility and was selected for the development of solid systems. Assays confirmed the production of true inclusion complexes between BNZ and HPβCD. The dissolution rate of the BNZ-HPβCD system was markedly increased, while the presence of HPMC retarded drug release. An optimal formulation obtained by the combination of kneading systems developed in appropriate ratios could be a promising drug delivery system with a prolonged therapeutic effect coupled with more balanced bioavailability. The produced systems present interesting perspectives for Chagas’ therapy.

Keywords::

• Chagas’ disease
• cyclodextrin
• dissolution profile
• drug control release
• hydroxypropyl methylcellulose

Acknowledgments

The authors would like to thank LAFEPE, Brazil, for their charitable donation of BNZ. The authors are also thankful for the generous gift of diluent samples from Colorcon^®, Brazil.

Declaration of interest

This work was supported by CNPq (Brazil; Project number 472134/2008-6).