Carla José

Enzymatic kinetic resolution of racemic ibuprofen: past, present and future.

Abstract This review is a journey concerning the investigations of the kinetic resolution of racemic ibuprofen for the last 20 years. The relevancy of the pharmacological uses of the S( + ) enantiomer along with its higher cost compared with racemic profen are the driving forces of a variety of scientific research studies addressing the enzymatic resolution of ibuprofen through enantiomeric esterification using lipases as biocatalysts. Lipases of fungal sources such as Candida rugosa, Rhizomucor miehei and the lipase B of Candida antarctica have been extensively studied both in homogeneous and heterogeneous (immobilized on solid supports) processes. In this context, the various alcohols and organic co-solvents frequently used in the esterification of racemic ibuprofen are summarized and discussed in this review. Moreover, recent investigations using membranes as reactors coupled with the separation of the desired product and microfluidic devices are presented. Finally, some guidelines about future perspectives regarding the technology of the kinetic resolution of profens and research niches are given.

Influence of the nature of the support on the catalytic performance of CALB: experimental and theoretical evidence

The immobilization of the lipase B of Candida antarctica (CALB) was carried out on various hydrophilic and hydrophobic supports through adsorption and covalent bond interactions. The catalytic performance of the biocatalysts was evaluated in the enantioselective esterification of R/S-ibuprofen with ethanol without co-solvents added. The present investigation demonstrates that the biocatalysts based on CALB immobilized by adsorption on hydrophobic supports (acrylic resin, polymethylmethacrylate, polystyrene, epoxy resin and polypropylene) exhibit higher conversion of ibuprofen and enantiomeric excess towards the S-enantiomer than CALB immobilized on hydrophilic materials. Additionally, the enzyme loading is a key factor influencing the conversion of the substrate regardless of the nature of the support material. A high enzyme loading is detrimental to the specific activity of the biocatalysts. Experimental and molecular modeling investigations provided evidence for the influence of water activity in the stereospecificity of the lipase.