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

Abstract

Abstract 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 (<15 min) compared to the conventional drug. In conclusion, the formulation of benznidazole as nanosuspension is an alternative that overcomes the unfavorable properties of the drug and presents posological versatility to optimize current pharmacotherapy, mainly in pediatric patients.