Nanoprecipitation in confined impinging jets mixers: Production, characterization and scale-up of pegylated nanospheres and nanocapsules for pharmaceutical use

Abstract

This work focuses on the investigation of the mechanisms of nanoparticles formation, through nanoprecipitation in micromixers. Polymer nanoparticles (including both nanospheres and nanocapsules) constituted by a PEGylated derivative of cyanoacrylate are considered. Nanoprecipitation is carried out in confined impinging jets mixers characterized by different sizes and geometries through solvent-displacement under different operating conditions (polymer initial concentration, oil initial concentration, mixing conditions). After solvent evaporation, nanoparticles are characterized in terms of their size distribution by dynamic light scattering and in terms of their surface properties via ζ potential measurements and X-ray photoelectron spectroscopy. The most relevant dimensionless numbers for scale-up are evidenced. Results suggest that nanospheres and nanocapsules are significantly different colloidal systems, whose formation is controlled by different mechanisms. The initial oil and polymer concentration and the inlet jet velocity turn out to be the most important operating parameters. Moreover results show that confined impinging jets mixers are very efficient in controlling the supersaturation (which is the driving force of nanoprecipitation) allowing for the fine tuning of the final particle size and surface properties. Some experiments are also carried out in a vortex mixer, with two confined (but not impinging) jets, for comparison purposes.