IBR   13079
INSTITUTO DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
Unidad Ejecutora - UE
artículos
Título:
Pharmaceutical development of a parenteral formulations and evaluation of the biological activity of the trypanocide drug benznidazole
Autor/es:
LAMAS, MARIA CELINA; VILLAGGI, LUCIANO; NOCITO, ISABEL; BASSANI, GUSTAVO; PASCUTTI, FERNANDA; ESTEBAN SERRA; SALOMON, CLAUDIO
Revista:
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Referencias:
Año: 2006 vol. 307 p. 239 - 343
ISSN:
0378-5173
Resumen:
Chagas disease, caused by Trypanosoma cruzi, is a major public health
problem in Latin America. According to the World Health Organization,
around 20 million people are infected and another 40 million are at
risk of acquiring the disease. One of the drugs most frequently used
for the treatment of Chagas disease is benznidazole (BZL). It is
practically insoluble in water (0.4 mg/ml), which precludes the
preparation of liquid dosage forms, in particular, parenteral
formulations. Thus, the aim of this work was to investigate the
solubilization of BZL at two pH values using various cosolvents such as
ethyl alcohol, propylene glycol, polyethylene glycol 400, benzyl
alcohol, diethylene glycol monoethyl ether (Transcutol) and surfactants
such as polysorbates (Tween) 40 and 80, and sodium dioctyl
sulfosuccinate (AOT). Solvent systems based on PEG 400, with the
addition ethyl alcohol and/or potassium biphthalate buffer solution,
increased the BZL solubility up to 10 mg/ml. These alcoholic vehicles
showed no toxicity against parasite when assayed at 1%. Physical and
chemical stability studies showed that the formulations were stable for
at least 1.5 years. In agreement with the biological activity results,
the selected formulations are suitable for further clinical studies.
Moreover, increasing the aqueous solubility of BZL reduced the problems
in vitro testing techniques and bioassays leading to more reliable
results and/or reproducibility.