Enzymatic Deracemization of (R,S)-Ibuprofen Ester via Lipase-catalyzed Membrane Reactor

Abstract

Ibuprofen (isobutyl-propanoic-phenolic acid) is a chiral drug well-known for its analgesic, antipyretic, and anti-inflammatory effects. In the present work, an enzymatic membrane reactor (EMR) has been developed for the production of optically pure (S)-ibuprofen acid. The EMR is equipped with a multitubular fixed bed racemization unit to enhance the enzymatic deracemization of (R,S)-ibuprofen ester. Several process parameters such as enzyme loading, racemization catalyst loading, reaction temperature, buffer pH, as well as the flow rate were investigated. These experimental results were then compared with the proposed process model. It was found that the experimental data were in good agreement with the theoretical results. The optimum condition of the lipase-catalyzed dynamic kinetic resolution (DKR) using the EMR could give 96–98% conversion with 97–99% of product enantiomeric excess (ee p).

Biocatalyst Immobilization and Process Intensification: Production of (S)-Piperazine-2-carboxylic Acid Dihydrochloride

“…Several examples of continuous enantioselective hydrolysis employing immobilized enzymes have been reported, particularly as well at high substrate loadings. − As experienced in our batch mode experiments, the high K M for ( rac )- 2 , causing a decrease in the reaction rate at high conversions (40–50%) and product inhibition of 5 , has drawbacks, which could be addressed best via a continuous flow setup, particularly, as thereby a high substrate-to-catalyst ratio and the continuous removal of the product from 5 would be given features when running the reaction in a PBR. ,, …”

Advances in Bioprocess Technology

“…The substrate ((S)-ibuprofen ester) and the by-product (alcohol) were found to be uncompetitive and competitive inhibitors, respectively (Lau 2013;Sie Yon et al 2013). The reaction mechanism of the enzyme-catalyzed conversion of substrate (S) to product (P 0 ) is clearly illustrated in Fig.…”

“…The reaction media in the enzymatic membrane reactor (EMR) can be of aqueous, organic and two-liquid phases (organic-aqueous). The versatility of the two-liquid phases in hollow-fiber membrane reactor for DEKR for the production of (S)-ibuprofen acid has been investigated (Sie Yon et al 2013;Lau et al 2010). Polyacrylonitrile (PAN) has been used as membrane material due to its superior resistance to hydrolysis and oxidation.…”

Process Modeling Issues in the Design of a Continuous‐Flow Process for the Production of Ibuprofen

“…Supporting Information for this article can be found under DOI: 10.1002/ceat.202000371. This section includes additional references to primary literature relevant for this research [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46].…”