deoxycholic-acid and Parasitemia

This work aims to develop novel benznidazole (BZN) solid dispersions (SD) to improve its solubility and bioavailability properties. Low-substituted hydroxypropylcellulose (L-HPC) and sodium deoxycholate (NaDC) were evaluated as carriers. BZN solid dispersions containing different ratios of carrier were prepared by a freeze-drying process and characterized by SEM, powder X-ray diffraction (XRD), differential scanning calorimetry (DSC) and dissolution studies. The reduced BNZ crystallinity in the new formulations was confirmed by XRD, and supported by DSC. BNZ:L-HPC solid dispersion at a 1:3 ratio (w/w) (SD-1:3 L-HPC) improved the BNZ dissolution rate (85% at 5 min) in comparison with BNZ raw material (23% at 5 min). However, NaDC formulations showed a prolonged release (24% at 30 min for SD-1:3 NaDC), due to the formation of a sustained release matrix in acidic medium. In vivo studies performed in a murine model of Chagas disease showed that the formulation achieving the highest parasitemia suppression at a low dose of 25mg/kg/day after five days of treatment was SD-1:3 L-HPC (60% of parasitemia suppression versus 33% of suppression exerted by BNZ), suggesting that BNZ:L-HPC systems enhance the bioavailability of the drug.

Topics: Animals; Calorimetry, Differential Scanning; Cellulose; Chagas Disease; Chemistry, Pharmaceutical; Crystallization; Deoxycholic Acid; Drug Carriers; Female; Mice; Microscopy, Electron, Scanning; Nitroimidazoles; Parasitemia; Powder Diffraction; Trypanocidal Agents; X-Ray Diffraction