Lipase-catalyzed dynamic kinetic resolution of racemic ibuprofen ester via hollow fiber membrane reactor: Modeling and simulation

Abstract

The enantio-separation of racemic ibuprofen ester via enzymatic membrane reactor is studied. The lipase-catalyzed resolution technique integrates kinetic resolution (KR) with in situ racemization resulting in 100% optically pure product. A mathematical model of lipase-immobilized hollow fiber membrane reactor incorporating dynamic kinetic resolution (DKR) of racemic ibuprofen ester is proposed. In the process of developing theoretical models for DKR, two zones were considered: (i) enzymatic hydrolysis of substrate in membrane matrix support and (ii) simultaneous racemization of unreacted substrate outside the membrane. The first part of the modeling work emphasized on the derivation of DKR rate equations for both enantiomers, based on the enzymatic resolution mechanism. The second part of the DKR model was derived by considering the mass transfer in the DKR rate equation. The model was solved using two numerical methods by means of MATLAB ® build-in solver. The first numerical technique was based on the explicit Runge–Kutta to solve the system of non-linear first-order ordinary differential equations (ODEs) of DKR reaction rate. The second approach was a collocation technique for solving the non-linear second-order ODEs of the convective hydrolysis–racemization phenomena in the membrane layer. A number of process parameters were studied in order to investigate their effects on the concentration profiles and separation efficiency in terms of enantiomeric excess, i.e. ee s and ee p by simulating the models. The model parameters include Bodenstein number, B 0, Thiele modulus, Φ 2 and dimensionless racemization constant, γ. The simulation results showed that the hollow fiber membrane operates effectively at B 0 = 8.68, γ = 10, Φ 2 = 1 with ee s = 2% and ee p = 98.5%.