Modeling the gas antisolvent recrystallization process

A mathematical model describing the gas antisolvent recrystallization process has been developed. In this process, precipitation of a solid from solution is triggered through the addition of a dense gas antisolvent under near-critical conditions. The possibility of controlling the particle size distribution of the produced microparticles makes it rather attractive for pharmaceutical and biotechnology related applications. Using the precipitation of phenantrene from toluene due to carbon dioxide addition as a model system, a parametric analysis of the system has been carried out. Significantly different effects have been observed experimentally, going from a major dependence of the average particle size on the antisolvent addition rate to no dependence at all. This work confirms such behavior and clarifies that this is controlled by the relative weight of secondary nucleation with respect to primary nucleation. Moreover, it provides useful hints on how to develop and optimize the gas antisolvent recrystallization process for a new application.