Kinetic and equilibrium study of enantioseparation of propranolol in preparative scale chromatography

Abstract

In this study, heptakis(6-azido-6-deoxy-2, 3-di- O-phenylcarbamolyted) β-cyclodextrin (CD) bonded Chiral Stationary Phase (CSP) was synthesized and packed into semi-preparative columns, which were used to separate the β-blocker drug propranolol by high performance liquid chromatography (HPLC). A preliminary study determine the separation condition for the mobile phase which contained 60% buffer solution (1%TEAA, pH 4.5) and 40% methanol. The bed voidage, axial dispersion coefficient, overall mass transfer coefficients as well as equilibrium constants for the chromatographic enantiomeric separation were evaluated by moment analysis on the basis of solid film linear driving force model. Since SMB is preferably conducted in non-linear region to achieve higher productivity, it is more important to determine the competitive adsorption behaviour among the consisting species. To facilitate higher productivity for batch preparative and SMB separation of propranolol, competitive Langmuir isotherm was determined by h-root method. Simulated moving bed (SMB) separation of propranolol was performed based on the complete separation regions obtained from equilibrium and column parameters. The SMB experimental results confirm the validity of process parameters obtained in this study.