Anti-solvent precipitation of solid lipid nanoparticles using a microfluidic oscillator mixer

The mixing process is critical in the anti-solvent precipitation process of micro-/nanoparticles. It may directly determine the quality of particles, especially the size and uniformity. In this study, a previously developed microfluidic oscillator mixer is used for anti-solvent precipitation of solid lipid (Gelucire 44/14) nanoparticles. This micromixer generates high-frequency oscillatory flow to enhance the fluid mixing. Based on the design, high flow rates of up to 50 ml/min can be achieved to allow relatively high throughput production. Results show that, within a wide concentration range from 10 to 300 mg/ml, solid lipid particles of 50–240 nm can be produced with the polydispersity index ranging from around 0.16 to 0.26. The influences of the anti-solvent to solution flow rate ratio, the geometrical and operating parameters of the oscillator mixer including the secondary chamber depth, and pumping pressure are investigated. For comparison, the same process was also conducted using a static chaotic mixer. Relevant findings provide useful reference for the performance and potential applications of the oscillator mixer.