IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
artículos
Título:
Development and in vitro/in vivo evaluation of a novel benznidazole liquid dosage form using a quality-by-design approach
Autor/es:
SERRA, ESTEBAN; LEONARDI, DARÍO; SALOMON, CLAUDIO JAVIER; ALONSO, VICTORIA; REAL, DANIEL; SALOMON, CLAUDIO JAVIER; ALONSO, VICTORIA; REAL, DANIEL; SILBER, ARIEL MARIANO; SILBER, ARIEL MARIANO; ROCHA, SANDRA CARLA; ROCHA, SANDRA CARLA; SANTOS SOUZA, HIGO FERNANDO; SANTOS SOUZA, HIGO FERNANDO; SERRA, ESTEBAN; LEONARDI, DARÍO
Revista:
TROPICAL MEDICINE AND INTERNATIONAL HEALTH
Editorial:
WILEY-BLACKWELL PUBLISHING, INC
Referencias:
Año: 2017 vol. 22 p. 1514 - 1522
ISSN:
1360-2276
Resumen:
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 of benznidazole. 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.