Precipitation of Drug Particles Using a Gas Antisolvent Process on a High-Pressure Microfluidic Platform

A high-pressure microfluidic platform was used to mix an organic solution with carbon dioxide. Complete mixing occurred on board the microchip and allowed controlled precipitation of active pharmaceutical ingredients (APIs). Griseofulvin was precipitated from dimethylformamide with a tuneable particle size varying between 0.5 and 500 mu m. The particle size increased with API concentration (favorable crystal growth) and decreased with driving pressure (efficient mixing promoting nucleation). Two different micromixers were used: CO2 flowing into the solution from a side channel (T-junction) and CO2 entering the mixing channel flanked by two liquid streams (X-junction). Systematically smaller particles were obtained with the T-junction micromixer because of the higher antisolvent concentration. The process can be carried out continuously with good control over the operating parameters. It is a step in the miniaturization and process intensification of gas antisolvent precipitation with opportunities for micronizing APIs.