Preparation and characterization of Poloxamer 407 solid dispersions as an alternative strategy to improve benznidazole bioperformance

DAVIES, CAROLINA; PARADA, LUIS; SIMONAZZI, ANALÍA; GONZO, ELIO; CID, ALICIA G.; BERMÚDEZ, JOSÉ M.

JOURNAL OF PHARMACEUTICAL SCIENCES

JOHN WILEY & SONS INC

Lugar: New York; Año: 2018 vol. 108 p. 2829 - 2836

0022-3549

Benznidazole, the first line drug for Chagas disease treatment, presents a low solubility, limiting the possibilities for its formulation. In this work, solid dispersions´ technology was exploited to increase benznidazole kinetic solubility and dissolution rate, seeking for an improvement in its bioperformance. A physical mixture (PM) and a solid dispersion (SD) using Poloxamer 407 as carrier were prepared and characterized. Dissolution tests were performed and data were analyzed with the lumped model, which allowed to calculate different parameters of pharmaceutical relevance. A bioactivity assay was also carried out to probe the SD anti-trypanocidal activity. Among the most relevant results, the initial dissolution rate of the benznidazole SD was near 3, 4 and about 400-fold faster than the PM, a commercial formulation (CF) and an extracted benznidazole, respectivley. The times needed for an 80% of drug dissolution were 3.6 (SD), 46.4 (PM), and 238.7 min (CF); while the dissolution efficiency values at 30 minutes were 85.2 (SD), 71.2 (PM), and 65.0% (CF). Survival curves suggested that using Poloxamer 407 as carrier did not alter the anti-trypanocidal activity of benznidazole. These results allow to conclude that SDs can be an effective platform for immediate release of benznidazole in an oral administration.