Ian Clegg, an Associate Research Fellow at Pfizer Global Research and Development Sandwich Laboratories, United Kingdom recently posted a discussion on LinkedIn’s Process Analytical Technology (PAT) group site titled “PAT data (Mid-IR) posted onto YouTube.”
This YouTube video is entitled “Process Analytical Technology: Using Mid-IR spectroscopy to monitor a telescoped chemical reaction.”
In this video, 3 sequential chemical reactions are run in one vessel without stopping or isolating between reactions, and ReactIR™ (real-time in situ reaction analysis) is used to monitor all 3 reaction phases. All of the key reagents, intermediates and products produce unique peaks which show reaction progression without having to take samples. The video shows the spectra of the reaction as a function of time and how the spectra change. The video shows clearly which peaks were monitored and to which components those peaks correlate.
We always talk about ReactIR™ providing a “molecular video” recording of chemical reactions. I found the Pfizer PAT YouTube video to support this concept very clearly. The video is just under 4 minutes in length and has some very good annotations so that you can easily understand what is happening as the reaction progresses. There is even mention of an unstable reactive intermediate in “Reaction Phase 1.” I can imagine even without knowing all the details how valuable this information must be to have. Unstable intermediates are typically difficult, if not impossible, to characterize by offline analysis. Knowing when each of these reaction phases reaches steady-state allows the chemists to minimize batch time. Unstable intermediates can also decompose with time so minimizing batch times can also have a direct impact on minimizing the impurity profiles. In reaction phase 2, the annotation indicates that the reaction kinetics support the proposed reaction mechanism. This is a very good point and a industrial example of what we see quite commonly in publication – particularly from academia.
The conclusions made are that the reaction trajectory (progression) can be monitored continuously, that reaction times can be shortened, and that the appearance and disappearance of reactive intermediates can be monitored easily. Of course, the real value is in what this means to the business. I suspect that this translates into significant cost savings due to the shortened reaction times and potentially as well, improved quality as a result of having better information available in real-time.
Thanks to Ian Clegg and his colleagues at Pfizer for providing this very clear example of the value that real-time in situ FTIR can provide as a Process Analytical Technology (PAT) tool.
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