methylcellulose and Chagas-Disease

Benznidazole (BNZ) is traditionally used to treat Chagas disease. Despite its common use, BNZ has a poor water solubility and a variable bioavailability. The purpose of this study was to prepare BNZ microcrystals by solvent change precipitation and to study the effects of BNZ micronisation on therapeutic efficiency using a murine model of Chagas disease. The solvent change precipitation procedure was optimised in order to obtain stable and homogeneous particles with a small particle size, high yield and fast dissolution rate. The thermal and crystallographic analysis showed no polymorphic change in the microcrystals, and microscopy confirmed a significant reduction in particle size. A marked improvement in the drug dissolution rate was observed for micronised BNZ particles and BNZ tablets in comparison with untreated BNZ and commercial Rochagan. In vivo studies showed a significant increase in the therapeutic efficacy of the BNZ microparticles, corroborating the dissolution results.

Topics: Animals; Chagas Disease; Chemical Precipitation; Disease Models, Animal; Drug Compounding; Drug Delivery Systems; Excipients; Female; Hardness Tests; Hypromellose Derivatives; Methylcellulose; Mice; Nitroimidazoles; Polymers; Solubility; Solvents; Tablets; Trypanocidal Agents; Trypanosoma cruzi