Gas antisolvent crystallization of organic salts from aqueous solutions

The selection of process conditions for the crystallization of an organic s alt for pharmaceutical applications is studied in the present work. The cry stallization process is carried out using the gas anti-solvent (GAS) techni que to obtain particles with specific size and size distribution. The appli cation of this process to organic salt aqueous solutions requires the use o f cosolvents to increase the solubility of the antisolvent gas in the aqueo us 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. Fav orable 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 a ntisolvent agent. The particles morphology is found to be strongly dependen t on the feed capillary diameter. (C) 2000 Elsevier Science B.V. All rights reserved.