Chiral separation of β-blocker drug (nadolol) by five-zone simulated moving bed chromatography

Abstract

Nadolol, a β-blocker drug used in the management of hypertension and angina pectoris, has three chiral centers and is currently marketed as an equal mixture of four stereoisomers. Resolution of three of the four stereoisomers of nadolol was obtained previously by HPLC, with a complete separation of the most active enantiomer (RSR)-nadolol, on a column packed with perphenyl carbamoylated β-cyclodextrin (β-CD) immobilized onto silica gel. Continuous separation of enantiomer (RSR)-nadolol from its racemate (which is a ternary mixture in the Chromatographic system of this study) in both 2-raffinate and 2-extract configuration of five-zone SMB was studied. Same experimental setup was applied to both configurations by modifying SMB controlling program accordingly. Separation performances of the five-zone SMB were investigated for both 2-raffinate and 2-extract configurations and same safety factors were applied to investigate the effect of m 3-m 2 (or m 4-m 3) on the separation performance systematically. The desired enantiomer of nadolol can be produced with a high purity and yield in 2-raffinate configuration compared with that in 2-extract configuration. © 2004 Elsevier Ltd. All rights reserved.