Compact SMB chromatography for binary separation

A thesis submitted for the degree of Doctor of PhilosophyThis thesis consists essentially of theoretical and experimental developments in the field of continuous chromatography using small-scale units. Continuous chromatographic separation processes based on the Simulated Moving Bed (SMB) technology were first patented and applied in 1961 for a large number of separations in the petrochemical industry and later for sugar separation. However, in the last two decades,due to the patent expiration, the process has been gaining great interest in the separation/purification of products in fine chemical and pharmaceutical industries. The conventional SMB comprises several identical columns which are serially connected in either a closed- or open-loop configuration. In order to simulate the movement of a solid bed in opposite direction to the fluid, the positions of the input and output streams are shifted downstream by one column, at fixed intervals, in the direction of fluid flow. With the development of new and efficient equipment and stationary phases, several new schemes of operating that differ from the conventional one have emerged. These include new concepts such as Varicol, ModiCon and PowerFeed processes, which rely on the periodic modulation of certain process parameters during the switching interval to enhance the efficiency of the separation. These advances are pushing the trend for units with a small number of columns, since the overall setup is more economical. However, when these newly schemes are applied in practice the process becomes more complex, because of the increased degrees of freedom that must be optimized. It is also less robust and more difficult to operate because it is more demanding on hardware. This additional complexity requires highly versatile SMB equipment, advanced optimization tools and robust control procedures. Experimental tools to experimentally reproduce the periodic state of multicolumn countercurrent chromatography with just one column are developed; they are economic and fast methods of experimentally exploring different column configurations and cyclic operation policies,ideally suited for applied research studies but may also be useful in the early stages of development, optimization, and validation of a new chromatographic separation. The feasibility of the proposed single-column system is experimentally demonstrated for several different column configurations, which include both synchronous and asynchronous port switchings and flow modulated schemes. Following the potentialities of these new operating schemes, a novel SMB system for binary separation that employs only two-columns is developed. The designed two-column process uses both the port switching and the flow rates modulation procedure. The process is very versatile since the cycle itself is optimized and adapted to the difficulty of the separation and process specifications. Furthermore, a simplified extension of the two-column setup which relies on a minimum pump number configuration and on a uniform flowrate scheme is built-up; additionally a further development on these simplified setup is applied which effectively enhances the process with only the cost of a small increase on the setup equipment. Potentialities of this new unit are illustrated comparing it to setups using the same amount of stationary phase.Fundação para a Ciência e Tecnologia (FCT/MCTES

Optimal design and operation of compact simulated moving bed processes for enantioseparations

Simulated moving bed (SMB) chromatography is attracting more and more attention since it is a powerful technique for complex separation tasks. Nowadays, more than 60% of preparative SMB units are installed in the pharmaceutical and in the food in- dustry [SDI, Preparative and Process Liquid Chromatography: The Future of Process Separations, International Strategic Directions, Los Angeles, USA, 2002. http://www. strategicdirections.com]. Chromatography is the method of choice in these ¯elds, be- cause often pharmaceuticals and ¯ne-chemicals have physico-chemical properties which di®er little from those of the by-products, and they may be thermally instable. In these cases, standard separation techniques as distillation and extraction are not applicable. The noteworthiness of preparative chromatography, particulary SMB process, as a sep- aration and puri¯cation process in the above mentioned industries has been increasing, due to its °exibility, energy e±ciency and higher product purity performance. Consequently, a new SMB paradigm is requested by the large number of potential small- scale applications of the SMB technology, which exploits the °exibility and versatility of the technology. In this new SMB paradigm, a number of possibilities for improving SMB performance through variation of parameters during a switching interval, are pushing the trend toward the use of units with smaller number of columns because less stationary phase is used and the setup is more economical. This is especially important for the phar- maceutical industry, where SMBs are seen as multipurpose units that can be applied to di®erent separations in all stages of the drug-development cycle. In order to reduce the experimental e®ort and accordingly the coast associated with the development of separation processes, simulation models are intensively used. One impor- tant aspect in this context refers to the determination of the adsorption isotherms in SMB chromatography, where separations are usually carried out under strongly nonlinear conditions in order to achieve higher productivities. The accurate determination of the competitive adsorption equilibrium of the enantiomeric species is thus of fundamental importance to allow computer-assisted optimization or process scale-up. Two major SMB operating problems are apparent at production scale: the assessment of product quality and the maintenance of long-term stable and controlled operation. Constraints regarding product purity, dictated by pharmaceutical and food regulatory organizations, have drastically increased the demand for product quality control. The strict imposed regulations are increasing the need for developing optically pure drugs.(...

Advances in simulated moving bed : new operating modes : new design methodologies and product (FlexSMB-LSRE) development

Tese de doutoramento. Engenharia Química e Biológica. Faculdade de Engenharia. Universidade do Porto. 200

A Comprehensive Study Of Esterification Of Free Fatty Acid To Biodiesel In a Simulated Moving Bed System

Simulated Moving Bed (SMB) systems are used for separations that are difficult using traditional separation techniques. Due to the advantage of adsorption-based chromatographic separation, SMB has shown promising application in petrochemical and sugar industries, and of late, for chiral drug separations. In recent years, the concept of integration of reaction and in-situ separation in a single unit has achieved considerable attention. The simulated moving bed reactor (SMBR) couples both these unit operations bringing down the operation costs while improving the process performance, particularly for products that require mild operating conditions. However, its application has been limited due to complexity of the SMBR process. Hence, to successfully implement a reaction in SMB, a detailed understanding of the design and operating conditions of the SMBR corresponding to that particular reaction process is necessary. Biodiesel has emerged has a viable alternative to petroleum-based diesel as a renewable energy source in recent years. Biodiesel can be produced by esterification of free fatty acids (present in large amounts in waste oil) with alcohol. The reaction is equilibrium-limited, and hence, to achieve high purity, additional purification steps increases the production cost. Therefore, combining reaction and separation in SMBR to produce high purity biodiesel is quite promising in terms of bringing down the production cost. In this work, the reversible esterification reaction of oleic acid with methanol catalyzed by Amberlyst 15 resin to form methyl oleate (biodiesel) in SMBR has been investigated both theoretically and experimentally. First, the adsorption and kinetic constants were determined for the biodiesel synthesis reaction by performing experiments in a single column packed with Amberlyst 15, which acts as both adsorbent and catalyst. Thereafter, a rigorous model was used to describe the dynamic behaviour of multi-column SMBR followed by experimental verification of the mathematical model. Sensitivity analysis is done to determine robustness of the model. Finally, a few simple multi-objective optimization problems were solved that included both existing and design-stage SMBRs using non-dominated sorting genetic algorithm (NSGA). Pareto-optimal solutions were obtained in both cases, and moreover, it was found that the performance of the SMBR could be improved significantly under optimal operating conditions

Improvement in the design and operation of Bio-reactors and Bio-separators based on SMB Technology

Ph.DDOCTOR OF PHILOSOPH

Optimal operation of simulated moving bed and varicol processes for bio-separation

Master'sMASTER OF ENGINEERIN

Compact simulated countercurrent chromatography for downstream processing of (bio)pharmaceuticals

Dissertação para obtenção do Grau de Doutor em Engenharia Química e BioquímicaFundação para a Ciência e Tecnologia - PhD gran

Study of modified simulated moving bed systems for ternary separation

Ph.DDOCTOR OF PHILOSOPH