Design of Novel Nanoemulsion Formulations for Topical Ocular Delivery of Itraconazole: Development, Characterization and in Vitro Bioassay

Purpose: The objective of this study was to design and develop nanoemulsion formulationsof itraconazole (ITZ), a water-insoluble, potent antifungal drug using the spontaneousemulsification method, to improve the ocular delivery and achieve a sustained release of thedrug.Methods: The oil was selected on the basis of the ITZ solubility while the surfactant and cosurfactantwere selected based on the thermodynamic stability and globule size. Followingthe selection of components, a pseudo-ternary phase diagram was constructed for the mostpromising formulation (F11) using benzyl benzoate (BB) as the oil, Eumulgin CO40 as thesurfactant, and propylene glycol as the co-surfactant, by the design of experiments (DoE).Results: F7 and F11 formulations were found to have an average globule size of 223.5 ± 10.7 nmand 157.5 ± 14.2 nm, besides thermodynamic stability and suitable physicochemical properties.F11 possessed an almost seven-fold higher cumulative percentage of in vitro released ITZ, incomparison to ITZ aqueous suspension after 24 hours. The release data suggested that the bestfitted kinetical model for F11 and F7 was the Higuchi and Korsmeyer-Peppas model.Conclusion: The extended-release of the drug beside an acceptable amount of loaded ITZsuggested that nanoemulsion is suitable for the delivery of the ITZ.