Chapter 7: Kinetic Approaches for Faster and Efficient Process Development
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Published:17 Aug 2011
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Special Collection: 2011 ebook collection , 2011 ebook collection , 2011-2015 organic chemistry subject collectionSeries: Drug Discovery
S. P. Mathew, in Pharmaceutical Process Development: Current Chemical and Engineering Challenges, ed. J. Blacker and M. T. Williams, The Royal Society of Chemistry, 2011, ch. 7, pp. 138-159.
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Kinetic analysis and understanding the influence of various process parameters on kinetic behaviour constitutes a major component of the science involved in process development, robustness and scale-up feasibility studies. This chapter highlights some of the basic kinetic approaches which we found very effective in dealing with our day-to-day process development efforts, such as reagent selection, process optimization, robustness and scale-up analysis, and understanding mass transfer influences. Well-designed kinetic experiments to determine the rate-determining steps were found to be effective in design reagents and/or conditions, whereas analysing the rate of formation and depletion of various reaction components throughout the entire course of a reaction gave very valuable information on kinetic trends, mass transfer and robustness issues. “Fingerprinting” of reaction rates using heat flow measurements can provide quick insights into process characteristics and kinetic trends. Modern kinetic methodologies like reaction progress kinetic analysis can be effective for driving force analysis and also in studying catalytic reactions from robustness and mechanistic viewpoints. The reactor modelling approach can be useful for predicting the scale-up behaviour of a process, and also for identifying key reactor characteristics that could influence the performance of the process on scale.