Lipid nanoparticles production by supercritical fluid assisted emulsion–diffusion

In this work a supercritical technology is proposed to improve the classical emulsification/diffusion technology for lipid nanoparticles (LNs) production. The process is based on the emulsion diffusion method improved by the addition of a continuous supercritical fluid processing step to eliminate the organic solvent from the nanosuspension obtained. Different emulsion/diffusion formulations for stearic acid nanoparticles production were tested and, then, processed by supercritical continuous extraction at 80 bar and 45 °C (liquid/gas ratio of 0.1) in a packed column, obtaining an efficient benzyl alcohol elimination. Solvent residues less than 100 ppm were measured. Stearic acid nanoparticles were not extracted or damaged by the supercritical processing step, did not stick on the packing elements and showed mean diameters of 30–50 nm; a value of one order of magnitude smaller than the ones obtained by the conventional emulsion/diffusion technology with a recovery efficiency of 100%. Indeed, the fast and complete elimination of the benzyl alcohol around the nanoparticles reduced the aggregation phenomena responsible of larger lipid particle sizes obtainable by traditional process.