Online Reaction Monitoring and Evaluation of Kinetic Parameters for Dilute Reactions Using Refractive Index Measurements

Abstract

This work demonstrates the utility of an online refractometer technique as a simple and accurate tool for monitoring the progress of a reaction and determining its end-point. It is also shown that, for a dilute reaction, the change of refractive index due to reaction is proportional to the extent of reaction. The corresponding kinetic rate coefficient can also be evaluated, provided the kinetic model is known. This proposed methodology was subsequently applied to monitor and study the kinetics of two different model reactions, namely alkaline hydrolysis of methyl paraben and hydrolysis of acetic anhydride. Both reactions were performed in dilute solution and under pseudo-first-order reaction conditions. The rate coefficients determined from the present refractive index measurements were in agreement with those independently determined using calorimetric and spectroscopic methods. Replicate kinetic experiments were also performed in order to confirm the reliability of the present refractive index measurements. For known simple reactions which are repetitively performed, or for continuous online process monitoring of simple reactions, the present approach provides a convenient alternative to spectroscopic and/or calorimetric monitoring.

Generative PAT Fingerprint Approach for Verification of the Scale-Up of Pharmaceutical Processes

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