Nanoparticles production in continuous flow devices – Modelling and experimental insights into continuous flow-based processes
In this work, a general overview on nanoparticles formation processes is given from both modelling and experimental points of view. The key mechanisms are presented and identified, despite some of them are still under debate. Experiments investigated the effect of different good solvents, as well as the role played by the presence of active principles, and more detailed confirmations have been found out thanks to modelling efforts. Population balance modelling and computational fluid dynamics simulations got a deeper insight into the mechanisms and the good solvent effects that lead to nanoparticles formation. Simulations results confirm the trends experimentally observed. Future investigations can be carried out by means of classical molecular dynamics, in order to gain a better understanding of the nanoparticle’s formation dynamics.
Nanoparticles formation is a complex process and numerous are the investigations, either experimental or by modelling, that have been conducted, due to the wide range of applications (e.g., pharmaceuticals, cosmetics, biology, textile industry). Different techniques can be used to synthesize nanoparticles; in particular, continuous flow-based and scalable techniques received a lot of attention in the last decades (1–3). One of the most employed methods is represented by the so-called solvent displacement (4), also known as flash nanoprecipitation. It consists in mixing a stream of good solvent, in which a solute (e.g., polymer) and the active principle are dissolved, with a bad solvent, or anti- or non-solvent, in which they are immiscible. As soon as the mixing occurs, the role of the anti-solvent is to destabilize the mixture, inducing nanoparticles formation and precipitation.
It usually takes place in very small mixers, order of magnitude of millimetres. Among the most used mixers (5), it is worthwhile mentioning the Confined Impinging Jets Mixer (CIJM) (6) and the Multi-Inlet Vortex Mixer (MIVM) (7), schematically represented in Figure ...