Antifungal Activity and Stability of Fluconazole Emulsion Containing Ionic Liquids Explained by Intermolecular Interactions

Abstract

This research reports accelerated stability experiments, the evaluation of intermolecular interactions, and antifungal assays for fluconazole emulsions prepared using ultrasound (US) and magnetic stirring (MS) in the presence of ionic liquids derived from 1,n-(3-methylimidazolium-1-yl)alkane bromide ([CnMIM]Br; n = 12 or 16). The goals of the investigation are to quantify the stability, identify the forces that drive the formation and stability, and determine the antifungal activity of fluconazole-containing emulsions, and corroborate the data from our previous results that indicated that the emulsion based on [C16MIM]Br seemed to be more stable. In this study, accelerated stability experiments evidenced a considerable stability for the [C16MIM]Br emulsions at two temperatures (25 and 37 °C)—the instability index increased in the following order: US40% < US20% < MS. The 1H NMR data showed that the ILs interacts differently with medium-chain triglycerides (MCT). Two distinct interaction mechanisms were also observed for [C12MIM]Br and [C16MIM]Br with fluconazole, in which the latter formed more compact mixed aggregates than the former. The result was corroborated by diffusion data, which showed that ILs suffered a decrease in diffusion in the presence of fluconazole. The antifungal assay showed that emulsions containing ILs displayed superior activity compared with fluconazole alone. The emulsions also showed potent activity in inhibiting a resistant species (C. glabrata—CG34) to FLZ. All emulsions showed weak irritant potential in HET-CAM assay.