Organic solvent-free Benznidazole nanosuspension as an approach to a novel pediatric formulation for Chagas disease

Benznidazole —a class II/IV as per the Biopharmaceutics Classification System—is the drug of choice for treating Chagas disease; however, its low aqueous solubility is a limiting factor that reduces its dissolution rate in a conventional available dosage form, resulting in erratic bioavailability and high interindividual variability. Formulation as nanosuspension is an attractive and promising approach to solve these problems. Thus, a nanosuspension was designed and prepared by bead-assisted nano-milling followed by freeze-drying to obtain nanocrystals, which were exhaustively characterized in the solid state. The nanosuspension was obtained by a simple and robust method, with an average particle size of 459.1 ± 9.0 nm and polydispersity index of 0.23 ± 0.01. It exhibited high electrokinetic potential (-27.8 ± 0.6) mV·cm-2 and was physically stable for at least 90 days, both under refrigerated and room conditions. Nanocrystals disperse rapidly in water, and their aqueous solubility is 10-times higher than the intrinsic value. The doses of benznidazole from nanosuspensions dissolved rapidly and completely (