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

SERRA E.; LEONARDI D.; SALOMON C.; ALONSO V. ; REAL D. ; SILBER A.; ROCHA S. ; SOUZA H.

TROPICAL MEDICINE AND INTERNATIONAL HEALTH

John Wiley & Sons, Inc.

Año: 2017 vol. 22 p. 1514 - 1522

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 optimisation procedure was carried out to estimate the values of the factors leading to the maximum drug concentration. The formulations were analysed 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 optimised 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 parasitaemia 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 ofbenznidazole. The in vivo studies confirmed the suitability of the optimised such solutions to diminish both parasitaemia and mortality. Thus, this novel alternative should be taken into account for further clinical evaluation in all age ranges.keywords Chagas disease, benznidazole, co-solvency, solubility, in vivo study