Simulated moving bed (SMB) technology developed by UOP in early 1960s has expanded greatly in the last decade, finding new applications in the area of natural products, fine chemistry and pharmaceutical industry. SMB processes are periodic processes designed to operate in cyclic steady state (CSS) and, therefore, the correct determination of CSS is needed for the assessment of the SMB performance. Two approaches can be used for determination of CSS: the dynamic simulation until CSS is reached and direct prediction of CSS. The direct prediction of CSS could be obtained in two ways: (i) considering that at CSS the spatially distributed SMB unit state at the end of the cycle is identical to that at its beginning (Method 1); or (ii) considering that at CSS the spatially distributed SMB unit state at the end of a switching time interval is identical to the state at the beginning of the interval, apart from a shift of exactly one column length (Method 2). The mathematical models assume axial dispersion flow and linear driving force (LDF) approximation for intraparticle mass transfer. Mathematical models were solved using the g PROMS (general Process Modelling System) software package. Both approaches (dynamic simulation and direct CSS prediction) were applied to the prediction of cyclic steady state of SMB unit for 1,1?-bi-2-naphthol enantiomersseparation. The direct CSS predictions were compared with the standard dynamic simulation CSS prediction in terms of accuracy of SMB performance and computing time requirements; the Method 2 for CSS prediction is more efficient than the standard dynamic simulation.
Fig. 6 compares the experimental and model selectivities for the three mobile phase compositions and illustrates three different scenarios. For 100% methanol, selectivity is low and constant, which means that the separation of ketoprofen enan- tiomers hardly can be achieved using pure methanol as mobile phase. The common 20% ethanol/80% n-hexane mobile phase, despite its high selectivity for low concentrations, presents a strong decrease in selectivity with the increase of enan- tiomers concentrations. The better situation is obtained for 100% ethanol, where selectivity maintains high values even for high enantiomer concentrations. In conclusion, pure ethanol can be used for ketoprofen enantioseparation, presenting better perfor- mances than the common 20% ethanol/80% n-hexane mobile phase: it allows significantly higher enantiomer solubilities, lower retention times and significantly higher selectivities at high enantiomer concentrations. These are all aspects of utmost importance considering the preparative separation of ketoprofen enantiomers.
The performance of the ketoprofen enantiomersseparation by SMB technology is compared in Figure 6 for different mobile phase compositions using the Equilibrium Theory model. The separation region (see plot γ 3 x γ 2 ) for 20%ethanol/80%n-hexane has operating conditions considerable different from the ones obtained for the pure alcohol mobile phases (pure ethanol and pure methanol) due to the higher retention times. Comparing the separation regions for the three mobile phases, it can be concluded that, for the 20/80 composition, the separation region becomes quickly smaller with the increase of feed concentration. This is a sign of stronger non-linear behavior of the adsorption process and a reason for lower productivities.
side, these results are very different from the ones obtained for the separation of the ketoprofen enantiomers. The dimension of the separation regions progressively decrease with the decrease of the n-hexane content (increase of the ethanol content). Therefore, the best performance (bigger separation region) is obtained with a 10%ethanol/90%n-hexane composition through all feed concentration range. The performance parameters predictions also support the previous conclusions. Under preparative conditions, maximum productivity is achieved with the 10/90 composition, while solvent consumption does not significantly differ for all mobile phase compositions.
The quantification of the two enantiomers of MA was done by HPLC-DAD by a method developed and validated in our research group, based on a protocol previously reported in literature. The liquid chromatograph was a HPLC Elite LaChrom (VWR Hitachi) possessing a diode array detector (DAD) l-2455, column oven l-2300, auto-sampler l-2200 and pump l-2130. The analytical column was constituted by a sorbent LiChrospher 100 RP-18 (5μm) and cartridge LiChroCART 250-4 HPLC- Cartridge, linked to a 5 μm, 4 mm × 4 mm guard column with the same stationary phase. The analytical column was from Merck. The mobile phase was chiral and it was prepared by mixing 15 wt% of methanol and 85 wt% of ultrapure water, containing 2 mM of L-phenylalanine and 1 mM of CuSO 4 . Whenever necessary, the pH of the mobile phase was corrected to 4.00 by adding an aqueous solution of ammonia (5 wt%). The mobile phase was then filtered under vacuum using regenerated cellulose membrane filters (0.45 μm) and degassed in an ultrasound bath. The chromatographic separation was done under isocratic mode, at a flow-rate of 0.8 mL.min -1 for 20 minutes. The injection volume was 20 μL, the DAD detector measured at 270 nm, the column oven temperature was 22 ºC and the autosampler temperature was 25 °C. The quantification was based on a calibration curve previously determined (Appendix A), based on 8 standard solutions of known concentrations of each enantiomer (10 – 1000 mg.L -1 ) in water:methanol (85 wt%:15 wt%) against the corresponding peak areas. Each system was done in quadriplicate and at least two injections per sample were done.
consumption is SC50.40 l of mobile phase per gram The main problem of the SMB operation consists of racemic mixture processed. Comparing this last in choosing the best solid (switch time interval) and value to the one obtained by the optimization liquid flow-rates. The SMB / TMB package is an procedure, we conclude that the solvent consumption important learning and training tool used to predict was reduced in 33%. Unfortunately, this solvent the effect of operating variables on the process saving was obtained with a significant reduction in performance, and so the choice of these best con- the extract and raffinate purities. Table 9 compares ditions for the SMB operation. The regions for the experimental results obtained for the separation enantiomer separation can be numerically predicted, of chiral epoxide enantiomers by SMB chromatog- considering dispersion and mass transfer resistances raphy carried out by the referenced authors. phenomena. The mass transfer resistance phenom- Fig. 17 show the SMB experimental internal enon affects the separation region of both enantio- profiles at cyclic steady-state. Simulation results are mers.
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mixture to be separated and the eluent / desorbent, The key to a successful chiral separation by SMB which is the adsorbent regeneration agent. The outlet chromatography resides in two basic aspects: (1) streams are the extract, which should be enriched correct choice of operating conditions and (2) correct with the more strongly adsorbed component (A), and choice of the stationary phase. As for the first aspect, the raffinate, which should be enriched with the several techniques have been proposed [18–21] to weakly adsorbed component (B). These inlet / outlet design appropriate SMB operating conditions which ports are shifted one bed ahead in the direction of the enhance purities, recoveries, productivity and mini- fluid flow at regular time intervals (the rotation mize solvent requirements. Designed for high prod- period). This arrangement is equivalent to an actual uctivity separations, SMB units usually operate at movement of the solid adsorbent relative to the fluid high feed concentrations leading to non-linear com- flow with fixed inlet / outlet ports (see Fig. 1). This petitive adsorption behaviors. Therefore, modeling equivalent representation, the true moving-bed and simulation tools are of crucial importance before
The regions for enantiomer separation can be numerically predicted, considering dispersion and mass transfer resistances phenomena. The mass transfer resistance phenomenon affects the separa- tion region of both enantiomers. Moreover, this influence is emphasized when a high purity re- quirement is desired. The set of Figs. 5 – 7 provide a practical tool for choosing the better SMB operating conditions as a function of the feed flow-rate. The optimum is found following the path of equal extract and raffinate purities and will result from a trade-off between solvent consumption and adsorbent productivity, purity and recovery requirements, and system robust- ness.
The algorithm of  reaches ca. 75% of the coeffi- cients set to zero without audible distortion. Note that this result was obtained with audio signals sampled at 44.1 kHz, where a larger amount of frequential compo- nents are inaudible than in 16 kHz-sampled signals. This method was used as a pre-processing step in the ISS algo- rithm described in , which applies an ICA algorithm to each TF bin of a stereo mix, based on the assumption that there are at most two dominating sources in each bin. Since this sparsification increases the amount of TF bins without any active sources, which do not need to be separated, it reduces the computational complexity of the separation. Nevertheless, as pointed out by the authors, this sparsification procedure leads to a small improvement in separation quality because the bins for which a perfect separation is possible (zero to two sources) represent only 10% of the energy of the mix in the presented experiments, with mixtures of five sources each (real music tracks).
PERVAPORATION: A NON-CHROMATOGRAPHIC CONTINUOUS SEPARATION TECH- NIQUE. A brief discussion of the non-chromatographic continuous separation techniques is pre- sented emphasizing the pervaporation process. It makes interesting choices for implementing vari- ous preliminary operations of the analytical process in order to accommodate the raw sample to the measuring instrument. Discussions include the perceived advantages and disadvantages, the underlying principles of pervaporation process, the flexible module and fields of application. Keywords: separation technique; preconcentration; pervaporation.
Finally, we have Ferrari’s separation. For the first step, Ferrari N.V., which at the time was a fully owned subsidiary of FCA, was used to facilitate many of the merger transactions noted above during the restructuring. This step can be seen as an initial separation, since everything related to Ferrari, namely Ferrari S.p.A. 7 , was moved to Ferrari N.V. From Exhibit 17 you can see that the net result for FCA of this transaction is an increase in € 2,52 billion (7,9B – 5,1B – 0,28B) in the assets side of the balance sheet. FCA benefits from Ferrari’s initial restructuring by improving its debt ratio. Then, from the IPO, FCA will obtain the proceeds and consequently raise more capital; however, since Ferrari after the spin-off will be a separate entity, its powerful brand will no longer be associated with, or of assistance to FCA. As you can see in TN-Exhibit 1, FCA’s profit margin is very low 8 therefore in order to keep the business running and fund its business plan xxxv , this was a way to raise capital.
analysis and to obtain simpler extensions of the existing results in the 1D case. Here we get rid of that assumption and introduce the notion of column dis- tance of 2D convolutional codes in a more natural way. We present upper bounds on these distances and provide characterizations in terms of the properties of the sliding parity-check matrices of the code. These results allow to introduce the notion of Maximum Separation Set Distance Profile 2D convolutional code which can be considered as the 2D analog of the well-known class of Maximum Distance Profile (MDP) convolutional codes .
many applications. This is a huge advantage since the separation systems based on polymers, which had the disadvantaged of having short polarity gaps, can be improved by the addition of ILs to the systems. It is known that their good purification performance is justified by the specific and different interactions that distinct ILs can establish with different solutes/molecules. Furthermore, these new systems present better results than the conventional aqueous biphasic systems (ABS) with higher extraction efficiencies in the separation of bio compounds like testosterone, epitestosterone and BSA (bovine serum albumin) (63), among other (64). An example of a good ionic liquid is composed by cholinium ([Ch], the cation component of the IL), which presents low toxicity, and good biodegradability (65). The usage of ionic liquids in PHA extraction is still low, but has been continuously studied in order to improve current and develop new extraction processes.