Strategies for multicomponent separation of Nadolol stereoisomers by simulated moving bed and jo processes
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Financial support by the Portuguese R&D foundation FCT (Fundação para a
Ciência e a Tecnologia) and European Community through FEDER (project PTDC/EQUEQU/
119025/2010) is gratefully acknowledged. This work was co-financed by FCT/MEC and FEDER
under Program PT2020 (Project UID/EQU/50020/2013) and by QREN, ON2 and FEDER (Project
NORTE-07-0162-FEDER-000050).
The Simulated Moving Bed (SMB) chromatography is an interesting alternative
technique for the production of fine chemicals and pharmaceuticals. The pioneer
classical SMB concept was designed for the separation of binary mixtures or to the
recovery of one single component from a multicomponent mixture. In recent years,
this technology has undergone through several important technical developments,
allowing the exploitation of better preparative separation performances. The
introduction of a wide range of new and more powerful preparative stationary phases
allied to the development of new and more versatile strategies and modes of SMB
operation are now a reality. Several configurations have been proposed in order to
extend the SMB technology to the separation of multicomponent mixtures by using a
cascade of SMBs in series or other complex SMB related techniques like multi-zone
SMB, intermittent SMB and JO processes [1-3].
Nadolol is a pharmaceutical drug marketed as a mixture of its four stereoisomers and
its prescription is related with some severe risks such as heart failure. This four
component mixture will be used as a case study for the development of
chromatographic strategies for multicomponent separation. Recently, our research
group reported the pseudo-binary separation of nadolol stereoisomers by SMB
chromatography [4]. A SMB pilot unit with Chiralpak AD chiral stationary phase was
used to obtained the more retained stereoisomer 100% pure. A different strategy was
also recently published based on a three column intermittent SMB unit [5].
A new methodology for the design, optimization and experimental implementation of
the multicomponent separation will be introduced, including the use of different chiral
and achiral adsorbents, the screening and choice of the best adsorbent-solvent
combinations, and the use of different SMB operating modes and strategies.