360579 Mixing Modeling Applied to a Mass Transfer Limited Heterogeneous Reaction with Lithium Hydroxide to Scale Between Plant and Lab Which Was Used to Reduce Cycle Time and Solve Issues with Reaction Time Variation

Thursday, November 20, 2014: 10:35 AM
203 (Hilton Atlanta)
Christopher J. Morrison, Particle Sciences and Engineering, GlaxoSmithKline, King of Prussia, PA and Qunying Dai, GlaxoSmithKline

Lithium hydroxide (LiOH) is commonly used in synthetic organic chemistry as a base in hydrolysis reactions.  In many cases, LiOH is charged as a solid and in cases where solubility is limited, as in methanol, the kinetics of the reaction can be dictated by the mass transfer limitations; specifically, the dissolution rate of LiOH.  The focus of this work was to understand and remedy issues with extended reaction times and stalled reactions.  Plant batch records and equipment drawings were used to build models in order to predict the changes anticipated on scale and the mixing was scaled-down to the bench scale where it was combined with statistical design of experiments (DoE) to investigate the effect of particle size, agitation, addition time, and lot-to-lot variability on the kinetics of the hydrolysis reaction. As expected for a dissolution controlled reaction, the particle size of the LiOH and the rate of agitation were observed to have the greatest statistical impact on the reaction rate.

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