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 nano-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 the 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 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) as compared with microfluidisation (∼10 µg) and homogenisation (∼7 µg). Microchannel processing improved nanoemulsion stability and skin delivery over homogenisation, offering scalable, energy-efficient continuous manufacturing, although PIC remained superior overall.