CHIRAL SEPARATION OF PROPRANOLOL HYDROCHLORIDE BY SMB PROCESS INTEGRATED WITH CRYSTALLIZATION
Resolution of propranolol hydrochloride was studied in self-packed columns of perphenyl carbamoylated beta-cyclodextrin (beta-CD). Both bed voidage and linear equilibrium constants were evaluated from a series of linear elution chromatograms by moment analysis. A modified h-root method was used to determine the competitive Langmuir isotherm of propranolol hydrochloride in the nonlinear region. Continuous separation of the target enantiomer from its racemic mixture was studied by Simulated Moving Bed (SMB) chromatography in both linear and nonlinear region. Desired (S)-propranolol hydrochloride was produced in the raffinate product at a high purity.Solubility of propranolol hydrochloride was determined experimentally in methanol at different temperatures. Crystallization of propranolol hydrochloride from different initial composition solutions in the mixed solvent of methanol and acetone was also investigated with different product purity and yield. SMB productivity was further increased at the sacrifice of decreasing product purity. The obtained solution was further purified by crystallization process. Compared with direct crystallization which is only suitable for racemic conglomerate, the integrated process is especially suitable for the majority of chiral drugs which belong to racemic compounds as long as suitable and economic chiral stationary phases (CSPs) are available in the SMB separation.
XIN WANG YUE LIU CHI BUN CHING
Division of Chemical and Biomolecular Engineering School of Chemical and Biomedical Engineering Nanyang Technological University Singapore 637722
国际会议
天津
英文
263-281
2006-05-22（万方平台首次上网日期，不代表论文的发表时间）