Systematic evaluation of commercial oil phases for Kolliphor HS 15-based PIT nanoemulsion formation and stability

Kolliphor HS 15 is a pharmaceutically relevant non-ionic surfactant with potential for phase inversion temperature (PIT) nanoemulsion development, but its compatibility with structurally diverse pharmaceutical oils remains unclear. This study systematically screened eleven commercial oil phases using a unified PIT protocol. Formulations contained 30% (w/w) total oil plus surfactant, with surfactant-to-oil ratios from 6:1 to 0.5:1, and underwent two heating–cooling cycles between approximately 15 and 85 °C. Turbidity was monitored as a qualitative in-process optical indicator, and visually homogeneous emulsions were characterized for droplet size, polydispersity index (PDI), pH, zeta potential, and 30-day stability at 25 and 40 °C. Six oils—Canola oil, Labrafac Lipophile WL 1349, Labrafac PG, Kollicream DO, Kollicream IPM, and Kollicream OD—formed initially homogeneous PIT emulsions at one or more surfactant-to-oil ratios, whereas five oils failed under the tested conditions. Compatible oils were generally triglyceride-rich or relatively neutral ester-type oils, while incompatible oils more often contained accessible amphiphilic or ionizable groups. All successfully characterized emulsions had initial Z-average droplet sizes below 100 nm with low PDI values. Abrupt optical transitions during heating were associated with successful fine-emulsion formation, but turbidity was not used to assign a PIT temperature. Storage stability was strongly dependent on oil type and temperature and was not predicted by initial droplet size alone. Overall, oil-phase selection, rather than surfactant excess alone, governed PIT emulsion formation, droplet refinement, and short-term stability.