Investigation of Factors Influencing Formation of Nanoemulsion by Spontaneous Emulsification: Impact on Droplet Size, Polydispersity Index, and Stability.

Interest in nanoemulsion technology has increased steadily in recent years for its widespread applications in the delivery of pharmaceuticals, nutraceuticals, and cosmeceuticals. Rational selection of the composition and the preparation method is crucial for developing a stable nanoemulsion system with desired physicochemical characteristics. In the present study, we investigate the influence of intricate factors including composition and preparation conditions that affect characteristic parameters and the stability of the nanoemulsion formation prepared by the spontaneous emulsification method. Octanoic acid, capryol 90, and ethyl oleate were selected to represent oil phases of different carbon-chain lengths. We explored the impact of the addition mode of the oil-Smix phase and aqueous phase, vortexing time, Km (surfactant/cosurfactant) ratio, and the replacement of water by buffers of different pH as an aqueous system. The phase behavior study showed that the Smix phase had a significant impact on the nanoemulsifying ability of the nanoemulsions composed of oil phases of varying carbon-chain lengths. The mode of mixing of the oil-Smix phase to the aqueous phase markedly influenced the mean droplet size and size distribution of the nanoemulsions composed of oil phases as capryol 90. Vortexing time also impacted the mean droplet size and the stability of the generated nanoemulsion system depending on the varying carbon-chain length of the oil phase. The replacement of the water phase by aqueous buffers of pH 1.2, 5.5, 6.8, and 7.4 has altered the mean droplet size and size distribution of the nanoemulsion system. Further, the Km ratio also had a significant influence on the formation of the nanoemulsion system. The findings of this investigation are useful in understanding how the formulation composition and process parameters of the spontaneous emulsification technique are responsible for affecting the physicochemical characteristics and stability of the nanoemulsion system composed of oil of varying carbon-chain (C8-C18) length.