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 Ciência e a Tecnologia (SFRH/BD/137966/2018).info:eu-repo/semantics/publishedVersio

Hydrogen Production from Sorption Enhanced Biogas Steam Reforming Using Nickel-Based Catalysts

Hydrogen gas is a clean and sustainable fuel/energy carrier considered to be a possible alternative to fossil fuels. Sorption enhanced biogas steam reforming is a process which combines a CO2 adsorption unit with a hydrogen production unit. In the CO2 sorption section, CaO was selected as the adsorbent due to its high stoichiometric adsorption capacity. From the adsorption test, the highest adsorption capacity (0.2849 gCO2/gCaO) was achieved at a temperature of 873 K. Four types of bed arrangement were investigated using a feed gas with a CH4/CO2 ratio of 1.5, an S/C ratio of 3, a temperature of 873 K and at atmospheric pressure. The results indicate that the Type II system (Catalyst physical mixed with sorbent system packed in fixed bed quartz reactor, 0.8 g of 12.5 wt% Ni/Al2O3 mixed with 2 g of CaO) exhibits the highest improvement in CH4 conversion with the introduction of CO2 adsorption (93.0% and 81.7%, with and without CO2 sorption, respectively) and high purity hydrogen was produced (97.0% v/v and 62.3% v/v, with and without CO2 sorption respectively)

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