Impact of non-ionic surfactants on release kinetics, toxicity and colloidal characteristics of benznidazole self-emulsifying delivery system evidenced by flow field-flow fractionation

Chagas disease is the major cause of death by cardiomyopathy in Latin America. Benznidazole (BZN) tablets are the standard of care for Chagas disease, and recently, self-emulsifying systems (SEDDS) have shown promising efficacy as the BZN delivery system, particularly for pediatric use. However, the comparative effects of surfactants on the physicochemical properties of SEDDS have been poorly investigated to date. SEDDS formulations containing medium-chain triglyceride as the oil phase and soy lecithin were developed using three non-ionic surfactants: polysorbate 80, Labrasol, and Cremophor EL. Asymmetric flow field-flow fractionation (AsF4) coupled with multi-angle laser light scattering (MALLS) and dynamic light scattering (DLS) were originally used to characterize the size distribution and homogeneity of SEDDS. The hydrodynamic sizes of emulsion droplets obtained after self-emulsification in water were lower than 220 nm, and zeta potential values ranged from -43 mV to -63 mV for all SEDDS formulations. A detailed analysis of AsF4 fractograms showed that all SEDDS formulations vary in size distribution and structure depending on the surfactant used and the presence of BZN. These factors affect the formation of emulsion droplets, as well as their shape, mass distribution, and colloidal organization. The results indicate that kinetically stable nanoemulsions are spontaneously produced upon water dilution. All SEDDS formulations increased the in vitro dissolution rate of BZN compared to pure BZN under sink conditions, and surfactants influenced the release profile. Toxicity concerns arising from high surfactant concentrations should be investigated in future studies. This simple and low-cost BZN lipid formulation offers a potential alternative for treating Chagas Disease with easy and personalized dosing adjustments.