Analysis of the supersaturation and precipitation process with supercritical CO2

An antisolvent precipitation process was studied in which an ethanol solution of the model drug acetaminophen (paracetamol) was dispersed or mixed with supercritical CO2 in a nozzle at high Reynolds numbers. The acetaminophen concentrations of the saturated and effluent solutions were measured using an on-line dynamic solubility method. These solubilities allow supersaturation in the jet (pre-precipitation) and in the reservoir fluid (post-precipitation) to be determined independently. Process conditions of partial and complete miscibility were investigated and it was shown that above the mixture critical pressure the crystallization was determined by mixing and primary nucleation processes characteristic of liquid solutions. Analysis of supersaturation provided a simple and effective way of process optimisation based upon particle size and product yield.