Efficient Racemization of the Pharmaceutical Compound Levetiracetam using Solvent Free Mechanochemistry
Abstract
We present the racemization of an active pharmaceutical ingredient Levetiracetam using a novel approach. We demonstrate the design of a 100% solvent-free process that proceeds by high energy milling inside a regular mixer mill. The kinetics of the racemization process is drastically improved compared to the solution-based approach and illustrates the tremendous potential of mechanochemistry. In this study, we highlight the importance of mixing efficiency regarding data reproducibility, and we show, in particular, that water contamination has a negative impact on the reaction rate. Moreover, in-situ X-ray diffraction gives us first insight of the mechanisms involved at the solid state during the mechanochemical racemization process.
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