The ability of different surfactant mixtures (SM) (polysorbate 80/sorbitan monooleate, 5 to 10% w/w) with cosurfactants (CO) (benzyl alcohol, ethanol, and 2-methylpyrrolidone) to produce stable benznidazole (BNZ) loaded soybean oil (SO, 10 to 30% w/w) in water (O/tW) emulsions was well assessed. Statistical tests were performed to select the best procedure parameters (temperature, shake conditions, and order inversion phases), using a phase inversion technique (PIT). Phase behavior was assessed by the pseudo-ternary phase diagram at the best HLB (9.0). Physicochemical stability was assessed at different storage conditions (4°C, 25°C, and 45°C, with thermal stress of 24h at each temperature, 30days). Rheological measurements demonstrated that all SO emulsions exhibited pseudoplastic flow-type (n~0.5) liquid-like behavior (k~0.19) with the absence of storage modulus (G′) and a predominance of loss modulus (G″) even for the most concentrated emulsion (30% w/w SO), and confirmed stability regarding flocculation. The droplet size remained between 42 and 61nm (PDI inferior to 0.3). However, benzyl alcohol contributed to an increase in droplet size, while 2-methylpyrrolidone led to the smallest droplet size. BNZ showed a weak interaction with the oil phase, but stable SO in water emulsions was produced with small and uniform droplet size containing a soluble drug fraction about four times greater than its aqueous solubility.
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