Determination of the Competitive Adsorption Isotherms of Nadolol Enantiomers by an Improved h-Root Method

Abstract

Nadolol, a β-blocker used in the management of hypertension and angina pectoris, has three chiral centers and is currently marketed as an equal mixture of its four stereoisomers. Resolution of three of the four stereoisomers of nadolol was obtained 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. The h-root method without the introduction of dummy species was presented and applied to determine the nonlinear competitive Langmuir isotherms of the three components of nadolol. In this method, h-root transformation was applied directly to the n-component nonstoichiometric system, without introduction of dummy species. The experiments consist of linear elution and nonlinear frontal chromatography. The solid film linear driving force model was used to simulate the response of a column to a pulse injection in the nonlinear region. The experimental and simulated profiles matched well, which confirmed the validity of the obtained Langmuir isotherm coefficients. On the basis of the isotherm obtained, complete (1, 2) and (2, 3) simulated moving bed (SMB) separation regions were determined to separate the ternary mixture of nadolol into different fractions.