Scalable Nanoemulsion Formation of Lipophilic Active Ingredients via Low-Energy Phase Inversion

Nanoemulsions are widely recognized as versatile delivery platforms capable of stably loading lipophilic active ingredients. Although low-energy phase inversion methods enable nanoemulsion formation under ambient and low-shear conditions, their scalability and applicability in practical formulation environments remain insufficiently validated. Here, we develop oil-in-water (O/W) nanoemulsions via a low-energy phase inversion process and systematically investigate their composition-dependent formation, scalability, and formulation stability. By precisely tuning the composition of a mixed nonionic surfactant system, monodisperse nanoemulsions with an average droplet size of ~110 nm and a polydispersity index (PDI ≤ 0.20) are reproducibly obtained under ambient, low-shear conditions. The optimized nanoemulsions maintain their nanoscale dispersion characteristics over 30 days of storage and exhibit consistent droplet size and distribution upon scale-up to 1 L. Furthermore, the nanoemulsions retain structural stability when incorporated into polymer-based formulations under various temperature conditions and repeated thermal cycling. These results demonstrate that low-energy phase inversion enables a scalable and formulation-compatible nanoemulsion platform, providing practical guidelines for industrial formulation and manufacturing of delivery systems for lipophilic active ingredients.