Microfluidic processing of coarse emulsions: a scalable approach for nanoemulsion preparation in dermal drug delivery

Nanoemulsions are increasingly explored to enhance dermal drug delivery due to their nanoscale size. Microfluidic processing for nanoemulsion generation has attracted much attention but requires extensive optimisation. This study leverages 3D printed microfluidic chips for size reduction of a premixed emulsion as a scalable approach to fabricate cationic oil‑in‑water nanoemulsions loaded with ibuprofen (2%w/w) for dermal delivery. Phase inversion composition (PIC) and homogenisation were used as benchmark methods. Nanoemulsions comprising ethyl oleate, Tween® 80 and cetyltrimethylammonium bromide were optimised using PIC (∼33 nm) and subsequently used to prepare premixed emulsions (∼84 nm). Microfluidisation effectively reduced the droplet size of premixed coarse emulsions (∼57-67 nm), achieving size reduction comparable to that obtained using conventional homogenisation (∼62 nm). Varying the microchannel geometry in microfluidic chips and the flow rate did not significantly affect the nanoemulsion properties. Nanoemulsions prepared by homogenisation remained <200 nm for 3 months at 40°C and 12 months at 25°C, but they were less stable than those prepared via PIC and microfluidisation. Nanoemulsions produced via PIC exhibited higher skin permeation of ibuprofen (∼14 µg) compared with microfluidisation (∼10 µg) and homogenisation (∼7 µg). Microchannel processing improved nanoemulsion stability and skin delivery compared with homogenisation, offering scalable, energy-efficient continuous manufacturing, although PIC remained superior overall.