A simple confined impingement jets mixer for flash nanoprecipitation

2012004

Han, J.; Zhu, Z.; Qian, H.; Wohl, A. R.; Beaman, C. J.; Hoye, T. R.; Macosko, C. W. J. Pharm. Sci. 2012, 101, 4018–4023. 

Abstract

Johnson and Prud′homme (2003. AICHE J 49:2264–2282) introduced the confined impingement jets (CIJ) mixer to prepare nanoparticles loaded with hydrophobic compounds (e.g., drugs, inks, fragrances, or pheromones) via flash nanoprecipitation (FNP). We have modified the original CIJ design to allow hand operation, eliminating the need for a syringe pump, and we added a second antisolvent dilution stage. Impingement mixing requires equal flow momentum from two opposing jets, one containing the drug in organic solvent and the other containing an antisolvent, typically water. The subsequent dilution step in the new design allows rapid quenching with high antisolvent concentration that enhances nanoparticle stability. This new CIJ with dilution (CIJ‐D) mixer is a simple, cheap, and efficient device to produce nanoparticles. We have made 55 nm diameter β‐carotene nanoparticles using the CIJ‐D mixer. They are stable and reproducible in terms of particle size and distribution. We have also compared the performance of our CIJ‐D mixer with the vortex mixer, which can operate at unequal flow rates (Liu et al., 2008. Chem Eng Sci 63:2829–2842), to make β‐carotene‐containing particles over a series of turbulent conditions. On the basis of dynamic light scattering measurements, the new CIJ‐D mixer produces stable particles of a size similar to the vortex mixer. Our CIJ‐D design requires less volume and provides an easily operated and inexpensive tool to produce nanoparticles via FNP and to evaluate new nanoparticle formulation.