Infrared andRaman Spectroscopy for Process Development

Abstract

With the demands on improved pharmaceutical productivity and quality, as well as the regulatory encouragement on applying process analytical technology (PAT), PAT is becoming increasingly recognized and embraced by pharmaceutical companies in both research and manufacturing areas. In this article, benefits of popular PAT tools, FTIR and Raman, to process development and scale‐up of active pharmaceutical ingredient (API) have been demonstrated. Applications of FTIR for in‐line monitoring and control of hazardous reactions, such as hydrogenation, Grignard reaction, and reaction involving potent species, are illustrated to achieve robust and safe processes. Meanwhile, in‐line measurement of a solute concentration by FTIR spectroscopy has made it possible to realize the feedback control of a crystallization process. In addition, for a better understanding and engineering of crystallization processes, Raman spectroscopy has shown as a valuable asset to characterize and quantify polymorphs in crystallization processes both in situ and at real‐time.

First FT-Raman and 1H NMR comparative investigations in ring opening metathesis polymerization

“…Raman has obvious advantages over the IR absorption spectroscopy, a technique which along with Raman accomplishes the full vibrational characterization of a molecule [23][24][25][26]. The scattering FT-Raman is usually less complicated, and the interpretation of data is more straightforward, yet the Raman signal is frequently weaker than in FT-IR.…”

On‐Line Monitoring of Chemical Reactions by using Bench‐Top Nuclear Magnetic Resonance Spectroscopy

“…The most important techniques available today for on-line measurements are gas chromatography (GC) and high-performance liquid chromatography (HPLC), as well as near-infrared, Fourier-transform infrared (FTIR), Raman, ultraviolet (UV), and nuclear magnetic resonance (NMR) spectroscopies. [1][2][3][4][5] Of these methods, high-resolution NMR spectroscopy is believed to be one of the most sophisticated and powerful ones. Some of the advantages that make NMR spectroscopy very attractive for real-time studies are that it is highly chemically specific, sensitive to all chemical groups, and that the signal is directly proportional to molecular concentration, requiring only a simple calibration that is valid for every reaction and all solvents.…”

Process Development and Control with Recent New FBRM, PVM, and IR

“…[1][2][3][4]15 It has been used as a valuable tool to provide better understanding of synthetic processes and hence ensure the quality of drug substances. It also serves as a useful tool to monitor synthetic processes under hazardous or harsh conditions by avoiding sampling of potent reaction intermediates or compounds at high temperature and/or pressure.…”

“…1,2,5 With the online IR analyzer one can not only obtain kinetic information at an early stage of process development but also carry out online analysis during production. 2 IR spectrometers are widely used for either online, at-line, or offline measurements because they can be used to elucidate reaction mechanisms and obtain kinetic information for the design of robust processes, achieving safer process scale-up. 6 Recent advances in IR instrumentation have added more flexibility to the existing IR analyzers in the lab and at scale-up facilities.…”

“…Process analytical technology (PAT) has been widely applied in chemical synthesis or purification as a means to monitor reactions or crystallization in the laboratory and manufacturing sites. − , It has been used as a valuable tool to provide better understanding of synthetic processes and hence ensure the quality of drug substances. It also serves as a useful tool to monitor synthetic processes under hazardous or harsh conditions by avoiding sampling of potent reaction intermediates or compounds at high temperature and/or pressure.…”