Selective Enantioseparation of Racemic Amlodipine by Biphasic Recognition Chiral Separation System

Abstract

The biphasic recognition chiral extraction process was developed and applied to separate amlodipine enantiomer. The chiral extraction system contained tartaric acid derivatives in the organic phase and β-cyclodextrin derivatives in the aqueous phase. The effect of extraction equilibrium time and the influence of different types of tartaric acids, types of β-cyclodextrin derivatives, organic solvents, and buffer pH were investigated. The results indicated that hydroxypropyl-β-cyclodextrin (HP-β-CD) showed a higher recognition ability toward (S)-amlodipine than (R)-amlodipine while dibenzoyl-D-tartrate demonstrated the strongest ability among tartaric acid derivatives to bind with (R)-amlodipine. The distribution ratios for (S)-amlodipine (k_S) and (R)-amlodipine (k_R) gave optimum values at pH 5.0 of 16.54 and 0.78, respectively. Biphasic chiral recognition extraction has great significance for preparative separation of (S)-amlodipine. It can also be used to design and apply the enantioseparation process.

Keywords:

• enantioseparation
• (S)-amlodipine
• biphasic chiral extraction
• β-cyclodextrin derivatives

ACKNOWLEDGEMENTS

Thanks are also given to the Separation Laboratory, Department of Chemical Engineering, Faculty of Engineering, Chulalongkorn University, Bangkok, Thailand, for chemical and apparatus support as well as to the Government Pharmaceutical Organization (GPO), Thailand, for kindly supplying active pharmaceutical ingredients and all instruments for analysis and measurement.

FUNDING

The authors are sincerely grateful to the Ratchadaphiseksomphot Endowment Fund of Chulalongkorn University (RES560530019-FW), the Chulalongkorn University Dutsadi Phiphat Scholarship and the Chromatography and Separation Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University.