Search

Nadolol is a nonselective beta-adrenergic receptor antagonist (beta-blocker) pharmaceutical drug, widely used in the treatment of cardiovascular diseases, such as hypertension, ischemic heart disease (angina pectoris), congestive heart failure and certain arrhythmias. This drug is still being marketed as a mixture of four stereoisomers in spite of the clear evidences that only one of its four stereoisomers has the desired therapeutic effect. Preparative liquid chromatography is actually an accepted route in industry to obtain enantiomeric pure drugs. Today, the combining of different chromatographic technologies, such as fixed-bed and simulated moving bed together with the use of achiral and/or chiral adsorbents are an important improvement in performance of preparative separation of multicomponent chiral drugs into its single pure stereoisomers. This work confirms this improvement using the referred strategy with mobile phase composition optimization at both normal and reversed-phase mode. Different separation strategies were designed and optimized, enlarging the packing materials possibilities, from fully chiral (Chiralpak) to achiral (C18) combined with chiral separation. For each separation step, the optimization of the solvent composition was carried out with pure alcohol, alcohol-hydrocarbon and alcohol-water mixtures, all with a basic modifier (diethylamine), taking into account the strong basic nature of the nadolol. This work was financially supported by: Base Funding - UIDB/00690/2020 of CIMO - Centro de Investigação de Montanha and Base Funding - UIDB/50020/2020 of the Associate Laboratory LSRE-LCM, both supports by national funds through FCT/MCTES (PIDDAC). This work is also a result of: Project “AIProcMat@N2020 - Advanced Industrial Processes and Materials for a Sustainable Northern Region of Portugal 2020”, with the reference NORTE-01-0145-FEDER-000006, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Rami S. Arafah is supported by a PhD Grant of Fundação para a Ciência e a Tecnologia (SFRH/BD/137966/2018). info:eu-repo/semantics/publishedVersion

The separation and purification of high added value products by liquid chromatography is a very popular technique. The development of more stable and efficient stationary phases, together with the design of innovative and more flexible separation processes, enhanced the use of chromatographic processes, particularly at preparative and industrial scales through fixedbed and simulated moving bed (SMB) technologies. Fixed-bed and SMB techniques are more and more used in the separation of a wide range of products for the pharmaceutical, fine chemistry, biotechnology and food industries. In this context, one of the actual main challenges concerns the design and optimization of these chromatographic processes for challenging multicomponent separations. This includes the development of new and innovative chromatographic processes, combining different design strategies and modes of operation, with different types of stationary and mobile phases. This work was financially supported by: Base Funding - UIDB/00690/2020 of CIMO - Centro de Investigação de Montanha - funded by national funds through FCT/MCTES (PIDDAC), and Base Funding - UIDB/50020/2020 of the Associate Laboratory LSRE-LCM - funded by national funds through FCT/MCTES (PIDDAC). This work is also a result of: Project - Advanced Industrial Processes and -01- 0145-FEDER-000006, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Rami S. Arafah is supported by a PhD Grant of Fundação para a Ciência e a Tecnologia (SFRH/BD/137966/2018). info:eu-repo/semantics/publishedVersion