Antisolvent precipitation of lipid nanoparticles in microfluidic systems - A comparative study.

Microsystems offer promising possibilities to produce nanoparticles which can be used as carriers for poorly water-soluble active substances. The aim of the present study was to compare the preparation of lipid nanoparticles by precipitation in different microsystems: A segmented-flow micromixer, a high-pressure micromixer and the commercial NanoAssemblr platform with a staggered herringbone micromixer. A batch set-up served as reference experiment. Castor oil nanoemulsions prepared with polysorbate 80 as surfactant in the aqueous phase were in the size range of 36-160 nm. The particle sizes could be reduced to 43-93 nm when the surfactant was processed via the ethanolic phase. Furthermore, glycerol monooleate nanodispersions (65-141 nm) were manufactured with poloxamer 407 added as stabilizer via the aqueous phase. Deposition of lipid material in the segmented-flow micromixer could be reduced by a modification of the design. Preparation in the high-pressure mixer and in the herringbone mixer at high total flow rates resulted in the smallest particles for castor oil emulsions, but with bimodal distributions. The particle size of glycerol monooleate dispersions was smallest when prepared in the high-pressure micromixer and in the herringbone micromixer at a higher flow rate. In conclusion, microfluidic systems can be a useful tool to produce lipid nanoparticles.