Enzymatic resolution is a potentially powerful approach for the separation of the stereoisomers. Lipases and carboxyesterases have been extensively studied for this purpose. Many lipase substrates, complex molecules with chiral centers, are poorly soluble in water. Thus bioconversions must be performed in multiphase, emulsion-type enzyme reactors with three phases present--organic, aqueous, and immobilized enzyme. Multiphase and extractive membrane reactors, based on hollow- fiber modules, offer several engineering advantages over conventional reactors by promoting efficient mass transfer and simplifying phase and product separation. This Phase II proposal seeks to optimize membrane bioreactor performance (productivity and enzyme stability), demonstrate enzymatic resolution in a large-scale module, and conduct both a technical and economic evaluation of an integrated important analgesic, (S)-Ibuprofen. New drugs under development are increasingly more complex in structure and require, in many cases, more elaborate purification schemes. The body is highly specific in regard to the recognition of the three-dimensional structure (i.e., streoisomers) of a pharmaceutical and, therefore, the drug needs to be of high stereochemical purity for it to be active. Extensive research has been conducted on the use of enzymes for the separation of mixtures of steroisomers. However, the commercialization of this technology must overcome certain engineering roadblocks to be economically feasible. The use of a novel enzyme reactor, based on membranes, has been shown to successfully address many of these problems in Phase I studies. This Phase II proposal seeks to optimize membrane bioreactor performance, demonstrate enzymatic resolution in a large-scale system, and conduct both a technical and economic evaluation of an integrated, enzymatic-resolution process for the production of (S)-Ibuprofen.
