High internal vegetable oil nanoemulsion: D-phase emulsification as a unique low energy process

The development of nanoscale emulsions containing high concentration of vegetable oil and low concentration of surfactant is considered challenging in conventional low-energy processes such as the Phase Inversion Temperature (PIT) and Phase Inversion Composition (PIC) methods. For the first time, a stable 20-30 nm oil-inwater nanoemulsion, containing 40.0% (w/w) olive oil was obtained with 2.0% (w/w) single hydrophilic surfactant, applying D-Phase Emulsification (DPE) process in combination with the Box-Behnken statistical design. The preparation of control samples using the PIT and PIC methods resulted in the absence of emulsion formation under the same composition and conditions followed by the DPE process. As a variable influencing the mean particle size of the nanoemulsion in this specific process, the polyol was confirmed to be crucial as the fourth component. An isotropic phase was revealed in place of a liquid crystalline structure or conventional micro-emulsion phase, enabling easy dispersion of the high oil content in the oil-in-surfactant intermediate phase, during this process. The presence of an initial isotropic phase indicated that there is no need for a strict adjustment of the hydrophilic-lipophilic balance (HLB), nor of the initial water-in-oil phase as in conventional low. energy methods. The results obtained in the present study confirmed the unique feature of the DPE process, overcoming the limitation of conventional low energy methods, for the development of nanoemulsions with high vegetable oil content as a drug delivery system.