In-line indirect concentration measurement of ultralow dose API during twin-screw wet granulation based on NIR and Raman spectroscopy.

Autor: Galata DL; Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary., Domokos A; Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary., Démuth B; SeraNovo B.V., J.H. Oortweg 21, 2333 CH Leiden, the Netherlands., Záhonyi P; Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary., Fülöp G; Gedeon Richter Plc., Formulation R&D, Gyömrői u. 19-21, H-1103 Budapest, Hungary., Nagy ZK; Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary. Electronic address: zsknagy@oct.bme.hu., Nagy B; Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3., H-1111 Budapest, Hungary.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Oct 25; Vol. 664, pp. 124650. Date of Electronic Publication: 2024 Aug 28.
DOI: 10.1016/j.ijpharm.2024.124650
Abstrakt: Twin-screw wet granulation (TWSG) is a promising continuous alternative of pharmaceutical wet granulation. One of its benefits is that the components dissolved in the granulation liquid are distributed homogeneously in the granules. This provides an elegant way to manufacture products with ultralow drug doses. Near-infrared (NIR) and Raman spectroscopy are well-established process analytical technology (PAT) tools that can be used for the in-line monitoring of TSWG. However, their detection limit does not enable the measurement of components in the ultralow (i.e., ppm) range. In this paper, an indirect approach is presented that enables the real-time determination of the concentration of a drug in concentrations between 40 and 100 ppm by using the signal of an excipient, in this case, the polyvinylpyrrolidone (PVP). This component is also dissolved in the granulation liquid; therefore, it is distributed in the same way as the active ingredient. Results of HPLC measurements have proved that the models trained to quantify the concentration of PVP in real-time gave an accurate determination for the active ingredient as well (root mean squared error was 7.07 ppm for Raman and 5.31 ppm for NIR spectroscopy, respectively). These findings imply that it is possible to indirectly predict the concentration of ultralow dose drugs with in-line analytical techniques based on the concentration of an excipient.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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