Continuous Production of Lipid Nanoparticles by Ultrasound-Assisted Microfluidic Antisolvent Precipitation

Microfluidic processes are of interest for the production of pharmaceutical nanoparticles due to the uniform characteristics attainable by such devices. However, precipitation processes in microfluidic systems incur a high risk of fouling, which compromises their reliability for continuous operation. A robust ultrasound-assisted process is established for the precipitation of lipid nanoparticles in a microfluidic mixer. The results indicate that nanoparticles can be produced over several hours without clogging. An analysis of the products reveals a small number of micron-sized particles, but these did not disturb the process. Thus, in-process ultrasonication is effective at improving the reliability of microfluidic precipitation and preventing buildup of precipitates in the channels.

Automated summary

An ultrasound-assisted process has been successfully established for the precipitation of lipid nanoparticles in a microfluidic mixer, allowing for the production of nanoparticles without clogging over several hours. The analysis shows a small number of micron-sized particles, but they do not disrupt the process, improving the reliability of microfluidic precipitation and preventing the buildup of precipitates in the channels.