Gas antisolvent crystallization of organic salts from aqueous solutions

Abstract

The selection of process conditions for the crystallization of an organic salt for pharmaceutical applications is studied in the present work. The crystallization process is carried out using the gas anti-solvent (GAS) technique to obtain particles with specific size and size distribution. The application of this process to organic salt aqueous solutions requires the use of cosolvents to increase the solubility of the antisolvent gas in the aqueous phase. The solubility of lobenzarit has been measured in water, methanol and water + methanol mixtures. The low solubility of lobenzarit in organic solvents is taken into account in the selection of the process scheme. Favorable operating conditions are found on the basis of a group contribution with association equation of state coupled with a non-linear optimizer. The feasibility of the proposed scheme and operating conditions are confirmed by experimental studies in a high pressure crystallizer, using CO2 as the antisolvent agent. The particles morphology is found to be strongly dependent on the feed capillary diameter.