Kinetic Modeling of Batch Reaction Processes

Abstract

Kinetic models have been demonstrated to be useful in on-line batch monitoring systems. The ability to monitor a reaction in real time is invaluable to the production process of industrial and pharmaceutical products. However, it is not a commonly used technique, due to some of its limitations. Currently, a great deal of work has been done showing the ability of a kinetic model to accurately estimate the spectral profiles and concentrations of reaction systems as a function of time. Some models have even demonstrated the technique's ability to model the transitions of analytes during dissolution and crystallization processes, but little has been done to combine all of these processes into a flexible, robust modeling system that incorporates all of these processes simultaneously. The goal of this work is three-fold: (1) to demonstrate the ability of a kinetic model to cohesively model dissolution, reaction, and crystallization processes, (2) accurately predict the spectral and concentration information produced by the reaction system, and (3), to accurately model an actual industrial slurry reaction using these same methods. For first part of this work, an acetylsalicylic acid synthesis model system was chosen. This synthesis reaction contains all of the processes necessary to produce a cohesive model including dissolution of the salicylic acid reactant, simultaneous reaction of the reactants to form the product and side products, and subsequent crystallization and precipitation of the product. This work was performed using ATR-UV/Vis measurements to model changes in the solution phase of the reaction mixture and utilized HPLC measurements for validation of the results. The second part of this work used the same techniques seen in part one and extended them to a complex industrial slurry model system. This section of the work was performed using NIR reflectance measurements to model the changes in the solid phase of the reaction mixture. This portion also used HPLC measurements for validation purposes. The work done within these two sections demonstrates the ability of the kinetic model to operate in both in the solid and liquid state and using multiple spectroscopic methods.