Investigation on crystallization phenomena with supercritical carbon dioxide (CO2) as the antisolvent

Abstract

Abstract The supercritical antisolvent (SAS) recrystallization process is one of the most promising recrystallization techniques for the particle formation of pharmaceutical compounds. In this process, a solution of active pharmaceutical ingredient (API) is sprayed into the supercritical carbon dioxide (SC CO2) environment. The mass transport of both the solvent and the antisolvent results in supersaturation followed by the crystallization of the API. In this work, a model is developed to estimate the supersaturation profile of solute in a droplet falling in the SC CO2 environment. The droplet consists of paracetamol as a solute and ethanol as a solvent. It moves down in the antisolvent (supercritical CO2) environment. Interestingly, the present model predicts a rise in supersaturation followed by a fall for a while and then a sharp increase. The competing phenomena of nucleation and growth mechanisms are used to justify this variation in the supersaturation.