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Fast and non-destructive pore structure analysis using terahertz time-domain spectroscopy
Open accessAbstract
Pharmaceutical tablets are typically manufactured by the uni-axial compaction of powder that is confined radially by a rigid die. The directional nature of the compaction process yields not only anisotropic mechanical properties (e.g. tensile strength) but also directional properties of the pore structure in the porous compact. This study derives a new quantitative parameter, S a, to describe the anisotropy in pore structure of pharmaceutical tablets based on terahertz time-domain spectroscopy measurements. The S a parameter analysis was applied to three different data sets including tablets with only one excipient (functionalised calcium carbonate), samples with one excipient (microcrystalline cellulose) and one drug (indomethacin), and a complex formulation (granulated product comprising several excipients and one drug). The overall porosity, tablet thickness, initial particle size distribution as well as the granule density were all found to affect the significant structural anisotropies that were observed in all investigated tablets. The S a parameter provides new insights into the microstructure of a tablet and its potential was particularly demonstrated for the analysis of formulations comprising several components. The results clearly indicate that material attributes, such as particle size and granule density, cause a change of the pore structure, which, therefore, directly impacts the liquid imbibition that is part of the disintegration process. We show, for the first time, how the granule density impacts the pore structure, which will also affect the performance of the tablet. It is thus of great importance to gain a better understanding of the relationship of the physical properties of material attributes (e.g. intragranular porosity, particle shape), the compaction process and the microstructure of the finished product.
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THz-TDS has been demonstrated to measure porosity of rocks and pharmaceutical tablets and to analyze anisotropy of pore structures.
“This method has been demonstrated to measure the porosity of rocks [20] and pharmaceutical tablets [21,22,23] as well as to analyze the anisotropy of pore structures [18,24].”
From Measuring Open Porosity of Porous Materials Using THz-TDS and an Index-Matching Medium (2020) · cites this paper as [18]
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Metadata
- Authors
- Markl, D., Bawuah, P., Ridgway, C., van den Ban, S., Goodwin, D. J., Ketolainen, J., Gane, P., Peiponen, K.-E., & Zeitler, J. A.
- Affiliations
- University of Cambridge (GB)
- University of Eastern Finland (FI)
- Omya (Switzerland) (CH)
- GlaxoSmithKline (United Kingdom) (GB)
- Corresponding author
- Markl, Daniel
- Venue
- International Journal of Pharmaceutics
- Publisher
- Elsevier BV
- Published
- 2018-02
- Volume
- 537
- Issue
- 1-2
- Pages
- 102-110
- ISSN
- 0378-5173 (ISSN-L)
- OpenAlex
- W2775088375
- Cited by
- 42
- References
- 26
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 4 · 2023: 5 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 3 · 2018: 5
- FWCI
- 1.48
- Type
- journal article
- Language
- en
- Open access
- Locations
- International Journal of Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- UEF eRepo (University of Eastern Finland) (acceptedVersion)
- Strathprints: The University of Strathclyde institutional repository (University of Strathclyde) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by-nc-nd)
- Apollo
- Topics
- Physical Sciences › Engineering › Electrical and Electronic Engineering › Terahertz technology and applications
- Physical Sciences › Engineering › Computational Mechanics › Granular flow and fluidized beds
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Keywords
- tablets, pore structure, anisotropy, terahertz time-domain spectroscopy, granule density, particle size distribution, compaction, tablet microstructure, indomethacin, microcrystalline cellulose, disintegration, liquid imbibition, porosity
- MeSH terms
- Calcium Carbonate, Cellulose, Chemistry, Pharmaceutical, Excipients, Particle Size, Powders, Tablets, Tensile Strength, Porosity, Anisotropy, Terahertz Spectroscopy
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