Monitoring of Antisolvent Crystallization of Sodium Scutellarein by Combined FBRM–PVM–NIR

351

238

This multiauthor review article aims to bring readers up to date with some of the current trends in the field of process analytical technology (PAT) by summarizing each aspect of the subject (sensor development, PAT based process monitoring and control methods) and presenting applications both in industrial laboratories and in manufacture e.g. at GSK, AstraZeneca and Roche. Furthermore, the paper discusses the PAT paradigm from the regulatory science perspective. Given the multidisciplinary nature of PAT, such an endeavour would be almost impossible for a single author, so the concept of a multiauthor review was born. Each section of the multiauthor review has been written by a single expert or group of experts with the aim to report on its own research results. This paper also serves as a comprehensive source of information on PAT topics for the novice reader.

Section: Methods For Pat Based Process Monitoring and Controlmentioning

confidence: 99%

Assessment of Recent Process Analytical Technology (PAT) Trends: A Multiauthor Review

Simon

Pataki

Marosi

et al. 2015

351

238

“…Saleemi et al combined FBRM with attenuated total reflection ultraviolet/visible spectroscopy (ATR-UV/vis) in order to detect the crystallization of isomers . Simon et al applied the same combination, supplemented with bulk video imaging (BVI), while Liu et al used FBRM, particle video microscopy, and near-infrared spectroscopy (NIR) . Polymorphic transformations were also investigated with combined PAT tools …”

Section: Introductionmentioning

confidence: 99%

Real-Time Image Processing Based Online Feedback Control System for Cooling Batch Crystallization

Borsos

Szilágyi

Agachi

et al. 2017

“…In the FDA’s PAT definition , (“a system for designing, analyzing, and controlling manufacturing through timely measurements (i.e., during processing) of critical quality and performance attributes of raw and in-process materials and processes, with the goal of ensuring final product quality”), “analyzing” equates to the use of in situ analytical tools. A variety of analytical methods have been incorporated into the PAT toolbox for online process monitoring, including focused beam reflectance measurement (FBRM), − particle video microscopy (PVM), , infrared (IR) spectroscopy, ,− UV–vis spectroscopy, Raman spectroscopy, ,, nuclear magnetic resonance (NMR) spectroscopy, ,, and high-performance liquid chromatography (HPLC) . However, little information is provided on chemical structures by many of these measurements, which only give signals for characteristic functional groups, and this remains one of the barriers to the application of spectroscopy in PAT applications.…”

Section: Introductionmentioning

confidence: 99%

Online Inductive Electrospray Ionization Mass Spectrometry as a Process Analytical Technology Tool To Monitor the Synthetic Route to Anagliptin

Yan

Bain

et al. 2016

Inductive electrospray ionization (iESI) is an ambient ionization method that is particularly well-suited to online reaction monitoring. It allows the potential of electrospray mass spectrometry (MS) to be realized as a routine process analytical technology (PAT) tool to monitor practical synthetic reactions in real time. In this study, a synthetic route to Anagliptin (target API) was successfully monitored using online iESI-MS. Starting materials not seen by traditional reaction monitoring tools (HPLC-UV/Vis and GC-FID) were observed, as well as water-sensitive reagents and intermediates which cannot easily be followed by other methods. Online tandem mass spectrometry (MS/MS) was used to characterize chemical species in the reaction mixture. Impurities and byproducts were identified, and information on the progress of byproduct formation enabled implementation of strategies to eliminate these byproducts in the course of the reaction. This work demonstrates how iESI-MS can be employed to obtain comprehensive information and solutions to some practical problems that occur in small-molecule synthetic reaction monitoring.