Novel cosolvent systems for nifurtimox: improving solubility, trypanocidal efficacy, and stability

BEDOGNI GISELLE; AZCARATE FEDERICO; GUERRA LUCINA; BOSCHETTI CARLOS; SERRA ESTEBAN; SALOMÓN CLAUDIO

VETERINARY THERAPEUTICS

Taylor & Francis

Año: 2025

1528-3593

ABSTRACTAim: This study aimed to evaluate a range of cosolvents and their mixtures as liquid vehicles toenhance the solubility and trypanocidal efficacy of nifurtimox.Materials & methods: Several pharmaceutical-grade solvents were screened for their ability to solubilizenifurtimox. The cytotoxicity of selected cosolvent systems was assessed and analyzed using the hemolysisassay. The stability of nifurtimox in these systems was studied under various temperature conditions. Thetrypanocidal activity of nifurtimox formulated in cosolvent systems was tested against Trypanosoma cruzitrypomastigotes by determining the drug concentration required to lyse 50% of the parasite population.Results: Nifurtimox solubility increased from 0.2 mg/mL in water to 23.5 mg/mL in selected cosolventsystems. Hemolytic assays indicated acceptable cytotoxicity profiles for the most promising formulations,supporting their suitability for further development. Trypanocidal studies demonstrated thatthese systems effectively inhibited or killed Trypanosoma cruzi trypomastigotes. Stability studies confirmedthatnifurtimox solutions remained chemically stable, with no precipitation and consistent drugcontent at all tested storage temperatures.Conclusion: Cosolvent-based delivery systems enhance the solubility of nifurtimox while maintainingadequate trypanocidal activity against Trypanosoma cruzi and demonstrating acceptable stability andsafety profiles. Thus, these formulations represent a promising strategy to improve the therapeuticeffectiveness of nifurtimox.