A comparative study for nanoparticle production with passive mixers via solvent-displacement: Use of CFD models for optimization and design

Active and passive mixers, including a considerable variety of micro-devices, are nowadays widely used for the production of nanoparticles. Polymer nanoparticles for controlled drug delivery applications are investigated in this work with two specific objectives. The first one is to experimentally quantify the efficiency of confined impinging jets reactors and Tee-mixers in the production of nanoparticles constituted by two polymers: poly-ɛ-caprolactone and poly(methoxypolyethyleneglycolcyanoacrylate-co-hexadecylcyanoacrylate). The second objective is the development of a simple and reliable mathematical model to be used for the design, optimization and scale up of mixers for polymer nanoparticle production. Although the behaviour of the polymers investigated is quite different, it is possible to conclude that confined impinging jets reactors are more efficient than Tee-mixers, in converting the pressure drop into turbulent kinetic energy and as a consequence in producing smaller particles. The very simple modelling approach proposed here (based on the evaluation of the mixing time) seems to be able to correlate well experimental data obtained under different operating conditions, independently on the type of device used. Moreover, in the case of poly-ɛ-caprolactone it was also possible to successfully quantify the particle formation time with a simple power law, further exploiting the model.

► This works investigates the use of micromixers for polymer nanoparticle production.
► Nanoparticles for pharmaceutical applications are produced with solvent-displacement.
► Micromixers with high flow rates results in small particles with narrow distributions.
► We use Computational Fluid Dynamics to quantify mixing efficiency.
► Successful design and scale up rules are derived and illustrated.