(124c) Use of Life Cycle Assessment to Evaluate the Sustainable Manufacture of the Active Pharmaceutical Ingredient Pregabalin

Three different routes to synthesize pregabalin, the active ingredient in the pain relieving medicine Lyrica^®, have been analyzed.  A life cycle assessment has been conducted to evaluate emissions generated from cradle to gate for the three syntheses.  The first process studied was a classical chemical synthesis resolution route.  The second manufacturing path involves the use of an enzyme to perform a biocatalytic resolution.  The third production path, also a biocatalytic route, integrates the recycle of a wrong enantiomer.  The analysis shows how transitioning from an entirely chemical synthesis to an enzyme-based biosynthesis greatly reduces organic solvent use and also the usage of the sponge Nickel catalyst.  A life cycle analysis associated with the raw materials used, energy consumed, and waste generated was performed.  Life cycle emissions resulting from the raw materials manufacture represent the majority of the carbon footprint for the three processes.  Upon using the biocatalytic process, the resulting amount of raw materials, waste and energy, and their respective carbon footprint are significantly reduced.  These changes are quantified and their contribution to the life cycle evaluated.  For example, the sponge nickel catalyst, is one of the largest contributors on a per mass basis and three times that of the lipolase enzyme, but small when the LCA is performed.  Organic solvents are a major contributor to the environmental footprint for the classical route.  Since the biocatalytic route is performed mainly in water, the majority of organic solvents are eliminated and their associated life cycle emissions are significantly reduced.