Scale-up of hydrogenation reactions can introduce mass transfer limitation, which can impact purity and yield in pharmaceutical scale-up. Knowledge of the gas-liquid mass transfer coefficient (kLa) and mass-transfer limit regime are necessary for reaction rate control during scale-up. However, correlations in literature for kLa are often inaccurate at predicting across various geometries and operating conditions. Therefore, experimental fitting for kLa is often employed. This presentation compares kLa fitting techniques across various geometries during a 1000x scale-up of a nitrobenzene to aniline reduction. Comparison of the techniques is made using kinetic reaction performance. Applicability of each technique is examined with respect to scale, reactor geometry, operating conditions, and analytical capabilities. This analysis enabled appropriate kLa fitting techniques to be employed for predictable and reproducible kinetics during scale-up from 3 g to 3 kg.
