Automated in-situ monitoring of accelerated crystallization processes of nifedipine using terahertz time-domain spectroscopy

Lara Heidrich; Julian Wiener; Enrique Castro-Camus; Martin Koch; Jan Ornik

doi:10.1038/s41598-024-81316-y

Automated in-situ monitoring of accelerated crystallization processes of nifedipine using terahertz time-domain spectroscopy

Sci Rep. 2024 Dec 2;14(1):29928. doi: 10.1038/s41598-024-81316-y.

Authors

Lara Heidrich^#¹, Julian Wiener^#², Enrique Castro-Camus^{2

3}, Martin Koch⁴, Jan Ornik^{2

5

6}

Affiliations

¹ Department of Physics and Material Sciences Center, Philipps-Universität Marburg, Renthof 5, 35032, Marburg, Germany. lara.heidrich@physik.uni-marburg.de.
² Department of Physics and Material Sciences Center, Philipps-Universität Marburg, Renthof 5, 35032, Marburg, Germany.
³ Centro de Investigaciones en Optica A.C, Loma del Bosque 115, Lomas del Campestre, Leon, Guanajuato, 37150, Mexico.
⁴ Department of Physics and Material Sciences Center, Philipps-Universität Marburg, Renthof 5, 35032, Marburg, Germany. martin.koch@physik.uni-marburg.de.
⁵ Leibniz Institute of Photonic Technology, Member of the Research Alliance, Leibniz Health Technologies, 07745, Jena, Germany.
⁶ Cluster of Excellence Balance of the Microverse, Friedrich Schiller University Jena, 07743, Jena, Germany.

^# Contributed equally.

PMID: 39622901
DOI: 10.1038/s41598-024-81316-y

Abstract

We developed and tested an automated measurement platform which can fit multiple samples for their investigation in transmission mode using terahertz time-domain spectroscopy. The temperature inside the platform can be varied to simulate different storage conditions of the samples, in our case, pharmaceuticals. As a proof-of-concept, the setup was successfully tested to monitor the crystallization process of amorphous nifedipine, as a model drug, at 24 °C, 30 °C and 35 °C for over 144 h. To the best of our knowledge, this is the first study to follow the crystallization of nifedipine with quasi-continuous measurements over a time frame of several days. The influence of the storage temperature on the crystallization rate was monitored including the appearance of polymorphic intermediate states of nifedipine throughout the process. The platform developed in combination with terahertz time-domain spectroscopy is a helpful tool for deepening the understanding of the crystallization behavior of amorphous and polymorphic materials and can be, for example, of great importance for the development of novel amorphous pharmaceutical formulations.

Keywords: Automatization; Crystallinity; Pharmaceuticals; Quality control; Terahertz spectroscopy.