236 research outputs found
Influence of mobile phase composition on the preparative separation of profens by chiral liquid chromatography
Liquid chiral chromatography of ketoprofen and flurbiprofen enantiomers is carried out using an amylose-based stationary phase. The mobile phases used for profens chiral separations are usually a hydrocarbon-alcohol combination, with high hydrocarbon content. However, profens show poor solubilities in hydrocarbon solvents when compared to alcohols. When the final objective is high productivity preparative separations, besides retention time, selectivity and column efficiency, solubility of the racemic drug is always a mandatory aspect to take into account. This work shows that an increase of the alcoholic content in the mobile phase is possible without a decrease in selectivity and column efficiency. Considering the chiral separation of ketoprofen and flurbiprofen enantiomers, results show that the mobile phase needs only a small quantity of acidic modifier and can be composed by a high or even pure alcoholic content. Additionally, it is found that the type of alcohol to be used can differ, depending on the profen racemic mixture to be separated
Chiral separation of nadolol stereoisomers by liquid chromatography : screening of mobile phase composition and SMB separation
This work describes a systematic approach to rapid development of simulated moving bed (SMB) chiral chromatographic separations. The presented methodology involves several pulse experiments using a single-column to screen the best mobile phase composition using a Chiralpak AD stationary phase and equilibrium adsorption data used to specify the initial flow rates of the SMB operation
Influence of mobile phase composition on the preparative separation of profens by chiral liquid chromatography
The chirality of drugs is an important issue for the pharmaceutical industry, since the different
enantiomers of a racemic drug may have distinct pharmacological activities, pharmacokinetic and
pharmacodynamic effects. Because of its chiral selectivity, human body reacts with a racemic drug
differently, and metabolise each enantiomer on separate pathways producing different
pharmacological activity. Thus, one isomer may produce the desired therapeutic activities, while the
other may be inactive or even, in worst cases, produce unwanted effects.
Flurbiprofen [2-(2-fluoroo4-biphenyl)-propionic acid] and ketoprofen [2-(3-benzoylphenyl)-propionic
acid] belong to a family of chemicals named 2-arylpropionic acids, or profens, an important sub-class
of the frequently prescribed and used drugs called nonsteroidal anti-inflammatory drugs (NSAIDs). A
considerable number of these drugs possess antipyretic activity in addition to its analgesic and antiinflammatory
actions, and thus have utility in the treatment of fever. The main primary indications for
NSAIDs therapy include rheumatoid arthritis, osteoarthritis, acute gouty arthritis, ankylosing
spondylitis and dysmenorrhea (DeRuiter, 2002). The importance of this class of drugs is supported by
U,e fact that, in the last twenty years, drugs like aspirin, phenazone derivatives or acetaminophen are
being supplemented by profens (Brune and Hinz, 1998)
Complete design and optimization of multicomponent separation processes: the case study of the quaternary separation of nadolol stereoisomers
The direct chromatographic resolution of enantiomers using chiral stationary phases (CSPs) is actually a very
well established separation technique. Several reasons were responsible for the growing success of this
technique. The continuous technical development of new chiral stationary phases (CSPs) combined with their
commercial availability has been, probably, the most relevant leverage issue.
Chiral liquid chromatography is based on different mutual interactions between the molecules that elute with the
liquid (solvent and solutes) and the molecules that are present in the stationary phase. Therefore, optimization of
a chiral separation is based on the selection of a proper combination between a CSP and a mobile phase (solvent)
composition by promoting, in a favourable way, all possible mutual interactions. The optimization will be a
much more challenging task if we are leading not with a traditional binary racemic mixture separation problem
but if we are interested in the separation of a quaternary chiral mixture. The complexity degree will be
significantly increased if we consider a preparative separation, using a technique such as the simulated moving
bed technology, were high feed concentrations are normally used in order to improve the process performance.
In these situations, the wanted high concentrations of the different chiral solutes inside the chromatographic
columns will enhance significantly the mutual competition between solutes for adsorption with the stationary
phase. From a preparative point of view, and when considering the choice of the mobile phase (“solvent”)
composition, a high selectivity of the enantiomers should not be the only goal to be aimed, as it is frequently the
case at analytical scale. Besides the choice of a CSP with high loading capacity, a high solubility of the solutes in
the solvent and low retention times should also be taken into account, in order to improve the preparative process
performance, as it was extensively explained for the separation of chiral non-steroidal anti-inflammatory drugs1-4
.
Nadolol (1-(tert-butyamino)-3-[(5,6,7,8-tetrahydro-cis-6,7-dihydroxy-1-naphthyl)oxy]-2-propanol) is a
non-selective beta-adrenergic antagonist pharmaceutical drug. This class of pharmaceutical drugs is prescribed,
mainly, to treat arrhythmias, angina pectoris, hypertension, migraine disorders and for tremor. Today, and in
spite of the more and more restricted international legislation towards the commercialization of pharmaceutical
drugs based on active principles that are made of single enantiomers, nadolol is still only commercially available
as an equal mixture of four stereoisomers. This is even more serious due to the considerable evidence, recently
made both by the academic community and pharmaceutical industry, that it is important to characterize the
single stereochemical components when describing the pharmacodynamics and pharmacokinetics of a racemic
drug.
The separation of nadolol stereoisomers on CHIRALPAK® AD at both analytical and preparative scales was
recently reportedby Ribeiro et al5. However, nowadays no further work was developed to better understand and
exploit the capabilities of Chiralpak® IA both for the analytical and preparative chiral separations of nadolol
stereoisomers. This work will present a complete methodology concerning experimental, modelling and
simulation results. Both the CHIRALPAK® AD and CHIRALPAK® IA CSP will be evaluated. The selection of
the proper CSP/solvent combination for preparative operation will be fully study taking into account the
screening strategy proposed by Zhang et al6. Additional results include the measurement of nadolol
stereoisomers solubilities, equilibrium adsorption data and fixed bed (breakthroughs) experiments. The complete
screening of CSP/solvent combination will lead to the choice of the better solutions for the separation of nadolol
stereoisomers, considering the target component or components to be obtained. Simulation and experimental
results will be presented for the multicomponent separation of nadolol stereoisomers by Simulated Moving Bed
adsorption process
Multicomponent chiral separations by analytical and preparative liquid chromatography
This work will present a complete methodology concerning experimental, modelling and simulation results. Both the CHIRALPAK AD and CHIRALPAK IA CSP will be evaluated. The selection of the proper CSP/solvent combination for preparative operation will be fully study taking into account the screening strategy proposed by Zhang et al. Additional results include the measurement of nadolol stereoisomers solubilities, equilibrium adsorption data and fixed bed (breakthroughs) experiments. The complete screening of CSP/solvent combination will lead to the choice of the better solutions for the separation of nadolol stereoisomers, considering the target component or components to be obtained. Simulation and experimental results will be presented for the multicomponent separation of nadolol stereoisomers by multicolumn and Simulated Moving Bed adsorption processes
Enantioseparation of the four nadolol stereoisomers by fixed-bed and simulated moving bed chromatography
In the last decades, the separation and purification of high added value products by liquid chromatography has been 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 simulated moving bed (SMB) technology and allied techniques. Nowadays, preparative and SMB related techniques are more and more used in the separation of a wide range of high added value products of interest 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 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 communication will introduce the multicomponent separation challenge using the commercial pharmaceutical drug of nadolol stereoisomers. The nadolol represents a very interesting case-study of multicomponent chiral separation since it is composed by four stereoisomers, arranged in two pairs of enantiomers. In this way, it introduces the possibility of alternative strategies, using different kind of separation sequences and techniques, the use of different packings (chiral and achiral stationary phases), and the correspondent mobile phase optimization at both normal and reversed phase modes.
An extensive set of experimental results obtained at fixed-bed and SMB operations will be presented. The complete methodology will be explained and applied for the pseudo-binary enantioseparation of the more retained and active stereoisomer (1+2+3)/(4), and for the (2)/(3) and (1)/(4) binary enantioseparations after a first achiral pseudo-binary separation of the two nadolol racemates.Financed by projects: NORTE-01-0145-FEDER-000006 - funded by NORTE2020 through PT2020
and ERDF; Associate Laboratory LSRE-LCM - UID/EQu/50020/2019 - funded by national funds
through FCT/MCTES (PIDDAC). Rami S. Arafah gratefully acknowledges his Ph.D. scholarship from
Funda~ao para a Ciencia e Tecnologia (FCT) SFRH/BD/137966/201B.info:eu-repo/semantics/publishedVersio
Coupled PermSMBR – Process design and development for 1,1-dibutoxyethane production
AbstractIn this work, a new configuration of the simulated moving bed membrane reactor (PermSMBR) technology is presented, the coupled PermSMBR, where the tubular membranes are located after fixed-bed columns packed with the catalyst/adsorbent. By this way the membranes are not in contact with the solid, which from an industrial point of view is easier to implement since the process of membranes installation/replacement and clean-up is simpler than in the previous considered set-up (tubular membranes packed with the catalyst/adsorbent – integrated PermSMBR). The 1,1-dibutoxyethane production is used, as an example, and the features of the new “coupled PermSMBR” and the previous set-up (integrated PermSMBR) are discussed. The coupled PermSMBR revealed to be a very attractive solution for the sustainable 1,1-dibutoxyethane production, proved by the high productivity and low desorbent consumption obtained within the studied conditions
Separation of nadolol racemates by high pH reversed-phase preparative chromatography
The separation of nadolol racemates under high pH reversed-phase preparative chromatography is presented for
the first time.
Three Waters C18 adsorbents (XBridge, Shield and XSelect) are compared for the separation of nadolol racemates
using ethanol:water:diethylamine solvent mixtures. Experimental and simulation results are presented
to compare the separation performances at preparative scale using both the fixed-bed and the simulated moving
bed operations.
The Waters XBridge C18 adsorbent and an ethanol:water:diethylamine solvent mixture are selected as a good
option for the separation of nadolol racemates. The validated methodology allows the separation of a multicomponent
nadolol feed mixture composed by four stereoisomers into two pure racemates (two pairs of enantiomers).
This work introduces the potential of using an initial achiral separation step in the global strategy for
the complete multicomponent separation of the four nadolol stereoisomers.This work is 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); Associate Laboratory
LSRE-LCM - UID/EQU/50020/2019 - funded by national funds through
FCT/MCTES (PIDDAC).
Rami S. Arafah is supported by a PhD Grant of Fundação para a
CiĂŞncia e a Tecnologia (SFRH/BD/137966/2018).info:eu-repo/semantics/publishedVersio
Complete separation of the quaternary mixture of nadolol stereoisomers using preparative and simulated moving bed chromatography
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.info:eu-repo/semantics/publishedVersio
Optimization of mobile phase composition for preparative separation of profens enantiomers by chiral liquid chromatography
In this paper it will be presented and discussed the experimental and simulation results obtained for the preparative separation of ketoprofen and flurbiprofen enantiomers by chiral liquid chromatography. Experimental results include solubility studies, elution and frontal chromatographic experiments and the measurement of competitive adsorption isotherms, using different mobile phase compositions. Modeling and simulation tools are used to predict the behavior and the performance of fixed bed and simulated moving bed processes. These prediction tools are used to select the proper mobile phase composition for the enantiomers separation in a preparative and production-scale point of view
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