Kinetics And Modelling For The Production Of (S)-Ibuprofen Acid
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Date
2012-06
Authors
Gonawan, Fadzil Noor
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Publisher
Universiti Sains Malaysia
Abstract
The effect of co-solvents and bases have been investigated in Candida rugosa lipase (CRL)-catalyzed hydrolysis of (R,S)-2-ethoxyethyl ibuprofen ester in biphasic water-isooctane medium. A high log P and low pKa values of co-solvent has reduced the reaction rate for the production of (S)-ibuprofen acid. Moreover, the hydrolysis process shows an optimum performance at only 2% (v/v) dimethyl sulfoxide (DMSO) and at the reaction temperature of 30°C. The addition of 2% (v/v) DMSO has increased the conversion of substrate and further increase in the concentration of DMSO has resulted in a low initial reaction rate and conversion of substrate, however gives a high enantiomeric excess of the product (eeP). Additionally, a higher differential activation enthalpy between (S)- and (R)-2-ethoxyethyl ibuprofen ester in the medium with 2% (v/v) DMSO has resulted in higher enantioselectivity. Moreover, the presence of DMSO has increased the CRL stability at higher substrate concentration in hydrolysis of (R,S)-2-ethoxyethyl ibuprofen ester.
A kinetic model to describe the behavior of the CRL in hydrolysis of (R,S)-2-etthoxyethyl ibuprofen ester was successfully developed by accounting the non-competitive inhibitor (2-ethoxyethanol), uncompetitive substrate inhibitor ((S)-2-ethoxyethyl ibuprofen ester) and competitive substrate inhibitor ((R)-2-ethoxyethyl
ibuprofen ester). The kinetic model was validated and able to estimate the kinetic constants. It has been found that, DMSO has reduced the Michaelis constant (KMA=384 mM), the maximum reaction rate (VAmax=4.5 mM/hr) and the inhibitors constant of non-competitive product inhibitor (KIP=140 mM), meanwhile the inhibitor constant of an uncompetitive substrate inhibitor (KISS=1950 mM) was increased.
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Keywords
Kinetics and modelling for the production , of (s)-ibuprofen acid