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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Development andin vitro/in vivoevaluation of a novel benznidazole liquid dosage form using a quality-by-design approach

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Autor(es):
Santos Souza, Higo Fernando [1] ; Real, Daniel [2, 3] ; Leonardi, Dario [2, 3] ; Rocha, Sandra Carla [1] ; Alonso, Victoria [4] ; Serra, Esteban [4] ; Silber, Ariel Mariano [1] ; Javier Salomon, Claudio [2, 3]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo - Brazil
[2] Univ Nacl Rosario, Area Tecn Farmaceut, Rosario, Santa Fe - Argentina
[3] Inst Quim Rosario, Rosario, Santa Fe - Argentina
[4] Univ Nacl Rosario, Area Parasitol, Rosario, Santa Fe - Argentina
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: TROPICAL MEDICINE & INTERNATIONAL HEALTH; v. 22, n. 12, p. 1514-1522, DEC 2017.
Citações Web of Science: 4
Resumo

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. (AU)

Processo FAPESP: 13/18970-6 - Caracterização do efeito Disulfiram em Trypanosoma cruzi
Beneficiário:Ariel Mariano Silber
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 16/06034-2 - O papel biológico de aminoácidos e seus metabólitos derivados em Trypanosoma cruzi
Beneficiário:Ariel Mariano Silber
Linha de fomento: Auxílio à Pesquisa - Temático