Characterization of the pore structure of functionalized calcium carbonate tablets by terahertz time-domain spectroscopy and X-ray computed microtomography
Open accessAbstract
Novel excipients are entering the market to enhance the bioavailability of drug particles by having a high porosity and, thus, providing a rapid liquid uptake and disintegration to accelerate subsequent drug dissolution. One example of such a novel excipient is functionalized calcium carbonate, which enables the manufacture of compacts with a bimodal pore size distribution consisting of larger interparticle and fine intraparticle pores. Five sets of functionalized calcium carbonate tablets with a target porosity of 45%-65% were prepared in 5% steps and characterized using terahertz time-domain spectroscopy and X-ray computed microtomography. Terahertz time-domain spectroscopy was used to derive the porosity using effective medium approximations, that is, the traditional and an anisotropic Bruggeman model. The anisotropic Bruggeman model yields the better correlation with the nominal porosity ( R 2 = 0.995) and it provided additional information about the shape and orientation of the pores within the powder compact. The spheroidal (ellipsoids of revolution) shaped pores have a preferred orientation perpendicular to the compaction direction causing an anisotropic behavior of the dielectric porous medium. The results from X-ray computed microtomography confirmed the nonspherical shape and the orientation of the pores, and it further revealed that the anisotropic behavior is mainly caused by the interparticle pores. The information from both techniques provides a detailed insight into the pore structure of pharmaceutical tablets. This is of great interest to study the impact of tablet microstructure on the disintegration and dissolution performance.
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Total porosity can be calculated from a THz-TDS measurement by using effective medium theory and knowing the intrinsic refractive index of the solid matrix.
“The total porosity can thus be calculated from a THz-TDS measurement by utilizing effective medium theory and knowing the intrinsic refractive index of the solid matrix.”
From Measuring Open Porosity of Porous Materials Using THz-TDS and an Index-Matching Medium (2020) · cites this paper as [23]
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 [23]
Previous THz-TDS approaches using effective medium theory or zero porosity approximation can determine total porosity from a THz waveform and known intrinsic refractive index.
“Previous studies have shown the measurement of the porosity of a sample using THz-TDS through the use of effective medium theory [23] or zero porosity approximation [30]. These approaches can determine the total porosity of a tablet from a THz waveform and the known intrinsic refractive index of the solid material.”
From Measuring Open Porosity of Porous Materials Using THz-TDS and an Index-Matching Medium (2020) · cites this paper as [23]
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Self-citation
- Authors
- Markl, D., Wang, P., Ridgway, C., Karttunen, A.-P., Chakraborty, M., Bawuah, P., Pääkkönen, P., Gane, P., Ketolainen, J., Peiponen, K.-E., & Zeitler, J. A.
- Affiliations
- University of Cambridge (GB)
- Omya (Switzerland) (CH)
- University of Eastern Finland (FI)
- Corresponding author
- Zeitler, J. Axel
- ORCID
- Venue
- Journal of Pharmaceutical Sciences
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 106
- Issue
- 6
- Pages
- 1586-1595
- ISSN
- 0022-3549 (ISSN-L)
- OpenAlex
- W2594867839
- Cited by
- 77
- References
- 33
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 5 · 2023: 9 · 2022: 7 · 2021: 11 · 2020: 16 · 2019: 9 · 2018: 8 · 2017: 3
- FWCI
- 4.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Pharmaceutical Sciences (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Aaltodoc (Aalto University) (submittedVersion, cc-by)
- UEF eRepo (University of Eastern Finland) (submittedVersion, cc-by)
- Strathprints: The University of Strathclyde institutional repository (University of Strathclyde) (submittedVersion, cc-by)
- UEF eRepo (University of Eastern Finland) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Apollo (cc-by)
- Funders
- University of Cambridge
- Engineering and Physical Sciences Research Council (EP/L019922/1)
- Topics
- Physical Sciences › Engineering › Electrical and Electronic Engineering › Terahertz technology and applications
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Physical Sciences › Engineering › Computational Mechanics › Granular flow and fluidized beds
- Keywords
- tablet porosity, pore structure, interparticle pores, intraparticle pores, effective medium theory, terahertz time-domain spectroscopy, X-ray computed microtomography, tablet microstructure, disintegration, dissolution, pharmaceutical excipients
- MeSH terms
- Calcium Carbonate, Excipients, Powders, Solubility, Tablets, Porosity, Anisotropy, Terahertz Spectroscopy, X-Ray Microtomography
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