In-line Fluorescence Spectroscopy for Quantification of Low Amount of Active Pharmaceutical Ingredient

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The pharmaceutical industry is currently implementing new manufacturing principles and modernizing the related processing solutions. A key element in this development is implementation of process analytical technologies (PAT) for measuring product quality in a real-time mode, ideally for a continuously operating processing line. Near-infrared (NIR) spectroscopy is widely used for this purpose, but has limited use for low concentration formulations, due to its inherent detection limit. Light-induced fluorescence (LIF) spectroscopy is a PAT tool that can be used to quantify low concentrations of active pharmaceutical ingredient, and recent development of instrumentation has made it available for in-line applications. In this study, the content of tryptophan in a dynamic powder flow could be measured as low as 0.10 w/w % with LIF spectroscopy with good accuracy of RMSEP = 0.008 w/w %. Both partial least squares regression and support vector machines (SVM) were investigated, but we found SVM to be the better option due to non-linearities between the calibration test and the in-line measurements. With the use of SVM, LIF spectroscopy is a promising candidate for low concentration applications where NIR is not suitable.

Original languageEnglish
JournalJournal of Pharmaceutical Sciences
Issue number9
Pages (from-to)2406-2410
Publication statusPublished - 2022

Bibliographical note

Funding Information:
Dan Henrik Sørensen, Niels Peter Aae Christensen, and Erik Skibsted are employed at Novo Nordisk A/S. Jukka Rantanen and Åsmund Rinnan have not received any consulting fees from Novo Nordisk A/S.

    Research areas

  • Fluorescence, Multivariate data analysis, powder mixtures, Process Analytical Technology

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