Reactor Kinetics Studies via Process Raman Spectroscopy, Multivariate Chemometrics, and Kinetics Modeling

Abstract

The deployment of in situ analytics for monitoring chemical reactions in process chemistry development and scale-up is facilitated by advanced instrumentation such as Raman spectrometry. Furthermore, greater process understanding can be engendered by coupling in situ Raman data with multivariate chemometrics analyses and kinetics modeling. Such information is important for devising science-based process control strategies along the concept of quality by design (QbD) initiated through the U.S. FDA process analytical technology (PAT) framework. A series of experiments using varied glass reactors, stirring speeds, and isothermal reaction temperatures were designed with acetic anhydride hydrolysis as the model reaction to successfully demonstrate the efficacy of combining in situ Raman spectroscopy, multivariate analyses, and kinetics modeling. Two different Raman measurement methods, using immersion and noncontact probe optics, were tested through a process Raman spectrometer with multiplexing capability. Information-theoretic multivariate chemometrics were applied to elicit pure component spectra and transient concentrations of chemical species, and two differential-algebraic equations modeling approaches were adopted for elucidating chemical and dissolution kinetics information. The variations in reactor vessel type and sizes, stirring speeds, Raman measurements, and kinetics models were compared in this study.

In situ monitoring of styrene polymerization using Raman spectroscopy. Multi‐scale approach of homogeneous and heterogeneous polymerization processes

“…One of the main current challenges is to design non invasive techniques able to catch different data about reactions media: molecular characteristics of macromolecules, size and shape of colloidal particles, macroscopic properties like viscosity… Ideally, the corresponding techniques should provide scalable data and should be suitable for adaptation to industrial equipments (for ultimate application to process and quality control). Two strategies could be proposed: continuous sampling coupled with fast analytical techniques on the one hand and in situ spectroscopic analyses on the other hand . Both approaches are complementary and we will particularly focus on the latter in that work.…”

“…Two strategies could be proposed: continuous sampling coupled with fast analytical techniques on the one hand [1] and in situ spectroscopic analyses on the other hand. [2] Both approaches are complementary and we will particularly focus on the latter in that work. Raman spectroscopy appeared as one of the most promising spectroscopic methods because of its fast response, its very low sensitivity to water, its applicability to both homogeneous and heterogeneous reaction media and the relative easiness of its use both at the laboratory scale and in industrial environment.…”

Process analytical technology: a critical view of the chemometricians

“…Powder samples are analyzed in , whereas API in intact tablets is predicted in . The possibility for elucidating chemical reaction information from the Raman data arrays is shown in . High selectivity to inorganic substances and polymorphs and low sensitivity to water make Raman spectroscopy a promising instrument for in‐line and on‐line process monitoring.…”

Monitoring the Caustic Dissolution of Aluminum Alloy in a Radiochemical Hot Cell Using Raman Spectroscopy

“…However, the quantification of multiple and/or confounding species in solution has been made possible by advancements in mathematical approaches such as multivariate regression analysis. 5–12…”