Development and in-vitro/in-vivo evaluation of a novel benznidazole liquid dosage form using a quality-by-design approach

SANTOS, HIGO ; REAL, DANIEL; LEONARDI, DARÍO; ROCHA, SANDRA CARLA; ALONSO, VICTORIA; SERRA, ESTEBAN; SILBER, ARIEL MARIANO; SALOMON, CLAUDIO JAVIER

TROPICAL MEDICINE AND INTERNATIONAL HEALTH

WILEY-BLACKWELL PUBLISHING, INC

Año: 2017

1360-2276

Objectives: To develop an alcohol-free solution suitable for children of benznidazole, the drug of choice for treatment of Chagas disease. Methods: In a quality-by-design approach a systematic optimization procedure was carried out in order to estimate the values of the factors leading to the maximum drug concentration. The formulations were analyzed in terms of chemical and physical stability and drug content. The final preparation was subjected to an in-vivo palatability assay. Mice were infected and treated orally in a murine model. Results: The results showed that benznidazole solubility increased up to 18.38 mg/ml in the optimized co-solvent system. The final formulation remained stable at all three temperatures tested, with suitable drug content and no significant variability. Palatability of the preparation was improved by taste masking of BZL. In-vivo studies showed that both parasitemia and mortality diminished, particularly at a dose of 40 mg/kg/day. Conclusion: Quality by design was a suitable approach to formulate a co-solvent system of benznidazole. The in vivo studies confirmed the suitability of the optimized such solutions to diminish both parasitemia and mortality. Thus, this novel alternative should be taken into account for further clinical evaluation in all age ranges.