Bordos, E., Das, G., Schroeder, S.L.M. orcid.org/0000-0002-4232-5378 et al. (3 more authors) (2025) Probing the interplay between drug saturation, processing temperature and microstructure of amorphous solid dispersions with synchrotron X-ray phase-contrast tomography. International Journal of Pharmaceutics, 669. 125018. ISSN 0378-5173
Abstract
The impact of drug saturation and processing regime on the microstructure of amorphous solid dispersions (ASDs) produced by hot-melt extrusion (HME) has been investigated. By exploring various combinations of drug loadings and processing temperatures, a range of drug saturation points were obtained by HME. The process was monitored with an in-line low-frequency Raman probe to construct the respective solubility phase diagram (i.e., solubility of crystalline drug in molten/soften polymer). The resulting ASDs were analysed with synchrotron X-ray phase-contrast micro computed tomography (Sync-XPC-μCT) in conjunction with a tailored image segmentation strategy to extract quantitative and qualitative descriptors. Despite minimal elemental variability between the drug (paracetamol) and the polymer (HPMC), Sync-XPC-μCT provided sufficient contrast to identify multiple structural domains, including drug-rich crystalline clusters, impurities, polymer-related heterogeneities and voids/pores. Supersaturated ASDs (> 20 wt% drug loading) displayed higher structural complexity and showed a plethora of highly defective API-rich crystalline domains upon ageing, which were absent in the undersaturated ASDs. Beyond its impact on the API physical state, the HME processing regime influenced the degree of homogeneity within the polymer fraction, as well as total porosity, size, shape and pore connectivity. By correlating with fundamental API-polymer solubility data, this study offers additional insight into the dynamics of the drug's solubilisation process during extrusion and the subsequent formation of microstructures within the ASD system, which have potential implications on product performance and stability.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Authors. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Amorphous solid dispersions; Hot-melt extrusion; Low-frequency Raman; X-ray phase-contrast tomography; ASD microstructure; API-polymer solubility |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemical & Process Engineering (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 08 Jan 2025 16:38 |
Last Modified: | 08 Jan 2025 16:38 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.ijpharm.2024.125018 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:221461 |