Enzymatic membrane reactors

In this case study, an enzymatic hydrolysis reaction, the racemic ibuprofen ester, i.e. (R)-and (S)-ibuprofen esters in equimolar mixture, undergoes a kinetic resolution in a biphasic enzymatic membrane reactor (EMR). In kinetic resolution, the two enantiomers react at different rates lipase originated from Candida rugosa shows a greater stereopreference towards the (S)-enantiomer. The membrane module consisted of multiple bundles of polymeric hydrophilic hollow fibre. The membrane separated the two immiscible phases, i.e. organic in the shell side and aqueous in the lumen. Racemic substrate in the organic phase reacted with immobilised enzyme on the membrane where the hydrolysis reaction took place, and the product (S)-ibuprofen acid was extracted into the aqueous phase. 

Long, W.S., Kamaruddin, A.H. and Bhatia, S. (2005) Enzyme kinetics of kinetic resolution of racemic ibuprofen ester using enzymatic membrane reactor. Chemical Engineering Science, 60 (18), 4957—1970. 

Long, W.S. Kamaruddin, A.H. andBhatia, S., Chiral Resolution of Racemic Ibuprofen Ester in an Enzymatic Membrane Reactor. Journal of Membrane Science., 2005, 247, 185-200. 

Recent studies in the pharmaceutical field using MBR technology are related to optical resolution of racemic mixtures or esters synthesis. The kinetic resolution of (R,S)-naproxen methyl esters to produce (S)-naproxen in emulsion enzyme membrane reactors (E-EMRs) where emulsion is produced by crossflow membrane emulsification [38, 39], and of racemic ibuprofen ester [40] were developed. The esters synthesis, like for example butyl laurate, by a covalent attachment of Candida antarctica lipase B (CALB) onto a ceramic support previously coated by polymers was recently described [41]. An enzymatic membrane reactor based on the immobilization of lipase on a ceramic support was used to perform interesterification between castor oil triglycerides and methyl oleate, reducing the viscosity of the substrate by injecting supercritical CO2 [42],... 

A very interesting field in membrane bioreactors is the production of cyclodextrins or oligosaccharides. In general, they have applications in food pharmaceutical, cosmetic agricultural, and plastics industries as emulsifiers, antioxidant, and stabilizing agents. In the food industry cyclodextrins are employed for the preparation of cholesterol-free products. The use of enzymatic membrane reactors to produce... 

The selection ofthe membrane to be used in enzymatic membrane reactors should take into account the size of the (bio)catalyst, substrates, and products as well as the chemical species ofthe species in solution and ofthe membrane itself. An important parameter to be used in this selection is the solute-rejection coefficient, which should... 

The first published information on the industrial application of a hybrid system with a HF contactor for production of the drug dilthiazem intermediate was reported by Lopez and Matson [23]. An enzymatic resolution of dilthiazem chiral intermediate is realized in an extractive enzymatic membrane reactor. The enzyme is entrapped in the macroporous sponge part of the hydrophilic hollow-fiber membrane made of a... 

Other Applications of One-Stage Enzymatic Membrane Reactors.273... 

When looking for an economically feasible enzymatic system, retention and reuse of the biocatalyst should be taken into account as potential alternatives [98, 99]. Enzymatic membrane reactors (EMR) result from the coupling of a membrane separation process with an enzymatic reactor. They can be considered as reactors where separation of the enzyme from the reactants and products is performed by means of a semipermeable membrane that acts as a selective barrier [98]. A difference in chemical potential, pressure, or electric field is usually responsible from the movement of solutes across the membrane, by diffusion, convection, or electrophoretic migration. The selective membrane should ensure the complete retention of the enzyme in order to maintain the full activity inside the system. Furthermore, the technique may include the integration of a purification step in the process, as products can be easily separated from the reaction mixture by means of the selective membrane. 

Enzymatic membrane reactors are classified in three main categories ... 

Fig. 10.3 Scheme of an enzymatic membrane reactor for the decolorization of the azo dye Orange II by manganese peroxidase... 

Table 10.3 Effect of MnP addition mode in dye decolorization (A) and efficiency (B) in the enzymatic membrane reactor with an Orange II concentration in the influent of 100 mg/L and HRT of 1 h...

Fig. 10.6 Experimental (open circle) and simulated data (Line) in the enzymatic membrane reactor with HRT of 72 min. Initial Orange II concentration 91.1 mg/L H202 addition rate 15 pmol/(L min)...

Lopez C, Moreira MT, Feijoo G et al (2007) Dynamic modeling of an enzymatic membrane reactor for the treatment of xenobiotic compounds. Biotechnol Bioeng 97 1128-1137... 

Lopez C, Mielgo I, Moreira MT et al (2002) Enzymatic membrane reactors for biodegradation of recalcitrant compounds. Application to dye decolourisation. J Biotechnol 99 249-257... 

Rios GM, Belleville MP, Paolucci D et al (2004) Progress in enzymatic membrane reactors -a review. J Membr Sci 242 189-196... 

Prazeres DMF, Cabral JMS (2001) Enzymatic membrane reactors. In Cabral JMS, Mota M, Tramper J (eds) Multiphase bioreactor design. Taylor Francis, London... 

Gumi T, Femandez-Delgado Albacete J, Paolucci-Jeanjean D et al (2008) Study of the influence of the hydrodynamic parameters on the performance of an enzymatic membrane reactor. J Membr Sci 311 147-152... 

Hernandez FJ, de los Rios AP, Gomez D, Rubio M, ViUora G. A new recirculating enzymatic membrane reactor for ester synthesis in ionic liquid/supercritical carbon dioxide biphasic systems. Appl Catal B 2006 67 121-126. 

Fig. 8.1 Experimental set-up of the recirculating enzymatic membrane reactor used for the synthesis of butyl propionate from vinyl propionate and 1-butanol catalysed by Candida antarctica lipase B in supercritical carbon dioxide and supercritical carbon dioxide/ionic liquid biphasic system [17]...

Hemdndez FJ, de los Rfos AP, Gomez D et al (2007) Understanding the chemical reaction and mass-transfer phenomena in a recirculating enzymatic membrane reactor for green ester synthesis in ionic Uquid/supercritical carbon dioxide biphasic systems. J Supercrit Flitids 43 303-309... 

The modelling of enzymatic membrane reactors follows, in general, the same approach as described previously. In enzymatic membrane reactors the catalyst is a macromolecule (enzyme). It can be found either in a free form in the reactor or supported on the membrane surface, or inside the membrane porous structure by grafting it or in the form of a gel obtained by ultrafiltration. As in the case of the whole-cell membrane bioreactors discussed above, the proper calculation of the mass transfer characteristics is of great importance for the modelling of this type of reactor. One of the earliest models of enzymatic membrane bioreactors is by Salmon and Robertson [5.108]. These authors modelled an enzymatic membrane bioreactor, which was made of four coaxial compartments the enzyme is confined within one of the compartments, and one of the substrates is fed in a gaseous form. 

Fig. 6.6.2 Schemritic diagrams of different configurations of enzymatic membrane reactors (a) stirred tank reactor with enzyme immobilized or retained by a membrane (b) stirred tank reactor coupled to ultrafiltration membrane...

Optimization of the Operational Parameters of the Enzymatic Membrane Reactor... 

Fig. 6.6.7 Orange II decolorization (white bars) and efficiency (grey bars) in the enzymatic membrane reactor at different strtitegies of MnP addition. Continuous addition of MnP was performed at 50,25 and 15 (xmol H2O2/L min...

A dynamic model was defined considering the kinetic equation and the hydraulics of the enzymatic membrane reactor. This model was validated comparing experimental data with model predictions at different experiments in steady-state conditions. Even when some modifications were performed, as changes in the Orange II concentration in the feed, the control system was able to predict the Orange II concentration in the reactor (Fig. 6.6.8). 

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