Preparative liquid chromatography is one of the most selective separation techniques in thefine chemical, pharmaceutical, and food industries. Several process concepts have beendeveloped and applied for improving the performance of classical batch chromatography. Themost powerful approaches include various single-column recycling schemes, counter-currentand cross-current multi-column setups, and hybrid processes where chromatography iscoupled with other unit operations such as crystallization, chemical reactor, and/or solventremoval unit. To fully utilize the potential of stand-alone and integrated chromatographicprocesses, efficient methods for selecting the best process alternative as well as optimaloperating conditions are needed.In this thesis, a unified method is developed for analysis and design of the following singlecolumnfixed bed processes and corresponding cross-current schemes: (1) batchchromatography, (2) batch chromatography with an integrated solvent removal unit, (3)mixed-recycle steady state recycling chromatography (SSR), and (4) mixed-recycle steadystate recycling chromatography with solvent removal from fresh feed, recycle fraction, orcolumn feed (SSR–SR). The method is based on the equilibrium theory of chromatographywith an assumption of negligible mass transfer resistance and axial dispersion. The designcriteria are given in general, dimensionless form that is formally analogous to that appliedwidely in the so called triangle theory of counter-current multi-column chromatography.Analytical design equations are derived for binary systems that follow competitive Langmuiradsorption isotherm model. For this purpose, the existing analytic solution of the ideal modelof chromatography for binary Langmuir mixtures is completed by deriving missing explicitequations for the height and location of the pure first component shock in the case of a smallfeed pulse. It is thus shown that the entire chromatographic cycle at the column outlet can beexpressed in closed-form.The developed design method allows predicting the feasible range of operating parametersthat lead to desired product purities. It can be applied for the calculation of first estimates ofoptimal operating conditions, the analysis of process robustness, and the early-stageevaluation of different process alternatives.The design method is utilized to analyse the possibility to enhance the performance ofconventional SSR chromatography by integrating it with a solvent removal unit. It is shownthat the amount of fresh feed processed during a chromatographic cycle and thus the productivity of SSR process can be improved by removing solvent. The maximum solventremoval capacity depends on the location of the solvent removal unit and the physical solventremoval constraints, such as solubility, viscosity, and/or osmotic pressure limits. Usually, themost flexible option is to remove solvent from the column feed.Applicability of the equilibrium design for real, non-ideal separation problems is evaluated bymeans of numerical simulations. Due to assumption of infinite column efficiency, thedeveloped design method is most applicable for high performance systems wherethermodynamic effects are predominant, while significant deviations are observed underhighly non-ideal conditions.The findings based on the equilibrium theory are applied to develop a shortcut approach forthe design of chromatographic separation processes under strongly non-ideal conditions withsignificant dispersive effects. The method is based on a simple procedure applied to a singleconventional chromatogram. Applicability of the approach for the design of batch andcounter-current simulated moving bed processes is evaluated with case studies. It is shownthat the shortcut approach works the better the higher the column efficiency and the lower thepurity constraints are.
展开▼
