Spatial and temporal visualization of polymorphic transformations in pharmaceutical tablets

Oswald, Iain and Gasol Cardona, Julia and Ward, Martin and Gutowski, Olof and Drnec, Jakub and Jandl, Christian and Stam, Danny and Maloney, Andy and Markl, Daniel and Price, Stephen (2024) Spatial and temporal visualization of polymorphic transformations in pharmaceutical tablets. Angewandte Chemie International Edition. ISSN 1521-3773 (https://doi.org/10.1002/anie.202412976)

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Abstract

X-ray Diffraction Computed Tomography (XRD-CT) represents a cutting-edge method for non-destructive material analysis, offering the unique capability of providing molecular-level information with spatial resolution. In this study, we have applied XRD-CT to investigate pharmaceutically relevant tablets that have been subjected to a range of compression pressures typical in tablet manufacturing. By employing XRD-CT to pharmaceutical tablets, we reveal material changes without tablet destruction, thereby avoiding potential phase transformations during sample preparation that could lead to errors in the interpretation of the processes that have occurred. Utilizing a pressure-sensitive marker, glycolide, we have tracked changes within tablet structures induced by compression, pinpointing locations where glycolide undergoes pressure-induced transformation. Additionally, we conducted a follow-up study with analysis one month later, observing an in-situ hydrolysis reaction of glycolide within the tablets. Through the complementary use of electron diffraction, we have elucidated the structure of the hydrolysis product, further enhancing our understanding of temporal changes in the tablets.

ORCID iDs

Oswald, Iain ORCID logoORCID: https://orcid.org/0000-0003-4339-9392, Gasol Cardona, Julia ORCID logoORCID: https://orcid.org/0009-0006-1249-3609, Ward, Martin ORCID logoORCID: https://orcid.org/0000-0003-0013-5004, Gutowski, Olof, Drnec, Jakub, Jandl, Christian, Stam, Danny, Maloney, Andy, Markl, Daniel ORCID logoORCID: https://orcid.org/0000-0003-0411-733X and Price, Stephen;
CORE (COnnecting REpositories)