Spontaneous nano-emulsification: Process optimization and modeling for the prediction of the nanoemulsion's size and polydispersity

The aim of the present study was to optimize the size and polydispersity of a lipid nanoemulsion as a function of the oil (Labrafac^® WL1349), surfactant (Kolliphor^® HS 15) and cosurfactant (Span^® 80) phase composition and temperature. The nanoemulsions were prepared using a low-energy self-emulsification method. The Z-average diameter and the polydispersity index (PDI) were modeled with mixture experiments. Nanoemulsions from 20nm to 120nm with PDI<0.2 were obtained at the three different tested temperatures (30°C, 50°C and 90°C). The nanoemulsion size was able to be controlled with the oil, surfactant and cosurfactant concentrations. Interestingly, the smallest PDIs were obtained at 30°C, and the cosurfactant concentration was able to be adjusted to optimize the formulation and to obtain nanoemulsions in the 20-120nm range with a PDI smaller than 0.14. These nanoemulsions have shown a good stability at 4°C in storage conditions and at 37°C in diluted conditions.