Characterisation of pore structures of pharmaceutical tablets: A review
Open accessAbstract
Traditionally, the development of a new solid dosage form is formulation-driven and less focus is put on the design of a specific microstructure for the drug delivery system. However, the compaction process particularly impacts the microstructure, or more precisely, the pore architecture in a pharmaceutical tablet. Besides the formulation, the pore structure is a major contributor to the overall performance of oral solid dosage forms as it directly affects the liquid uptake rate, which is the very first step of the dissolution process. In future, additive manufacturing is a potential game changer to design the inner structures and realise a tailor-made pore structure. In pharmaceutical development the pore structure is most commonly only described by the total porosity of the tablet matrix. Yet it is of great importance to consider other parameters to fully resolve the interplay between microstructure and dosage form performance. Specifically, tortuosity, connectivity, as well as pore shape, size and orientation all impact the flow paths and play an important role in describing the fluid flow in a pharmaceutical tablet. This review presents the key properties of the pore structures in solid dosage forms and it discusses how to measure these properties. In particular, the principles, advantages and limitations of helium pycnometry, mercury porosimetry, terahertz time-domain spectroscopy, nuclear magnetic resonance and X-ray computed microtomography are discussed.
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Porosity governs the mass transport processes and mechanical changes in tablets during disintegration and hence directly affects the dissolution time of tablets.
“Porosity governs the mass transport processes and mechanical changes in tablets during disintegration and hence directly affects the dissolution time of tablets.”
From Terahertz-Based Porosity Measurement of Pharmaceutical Tablets: a Tutorial (2020) · cites this paper as [46]
The Introduction says tablet void space controls liquid transport and that liquid uptake is often rate-determining for disintegration; it also describes swelling that ruptures interparticle bonds. Section 7.2 links porosity/density to disintegration time and the amount of drug dissolved after 15 minutes, but does not establish that porosity directly determines dissolution time. It instead says dissolution after disintegration is driven by the size of the resulting particles. (LLM, conf=0.83)
Experimental — accuracy not yet measuredPorosity is one of the most important contributors to tablet disintegration and dissolution characteristics.
“Porosity, a potential critical quality attribute (CQA) of tablets, is one of the most important contributors to tablet disintegration and dissolution characteristics [46].”
From Terahertz-Based Porosity Measurement of Pharmaceutical Tablets: a Tutorial (2020) · cites this paper as [46]
Porosity is a potential critical quality attribute (CQA) of tablets.
“Porosity, a potential critical quality attribute (CQA) of tablets, is one of the most important contributors to tablet disintegration and dissolution characteristics [46].”
From Terahertz-Based Porosity Measurement of Pharmaceutical Tablets: a Tutorial (2020) · cites this paper as [46]
The terahertz method is able to probe both connected and isolated pores whereas conventional methods like mercury porosimetry only capture connected pores.
“This is due to the fact that the terahertz method is able to probe both connected and isolated pores whereas conventional methods like mercury porosimetry only capture connected pores.”
From Terahertz-Based Porosity Measurement of Pharmaceutical Tablets: a Tutorial (2020) · cites this paper as [46]
The use of the THz-TDS method, which is conducted in the transmission configuration, has been demonstrated to accurately measure porosity of homogenous tablets compared to conventional methods like mercury porosimetry.
“Since porosity is a volumetric property, the use of the THz-TDS method, which is conducted in the transmission configuration, has been demonstrated to accurately measure porosity of homogenous tablets compared to conventional methods like mercury porosimetry [46].”
From Terahertz-Based Porosity Measurement of Pharmaceutical Tablets: a Tutorial (2020) · cites this paper as [46]
The inclusion of air in a compact lowers the measured refractive index.
“The inclusion of air in a compact lowers the measured RI [9].”
From Polymer Pellet Fabrication for Accurate THz-TDS Measurements (2022) · cites this paper as [9]
Sample porosity must be minimised because it affects the accuracy of the refractive index obtained from terahertz measurements.
“Sample porosity must be minimised as it affects the accuracy of the RI obtained from terahertz measurements [1,9,10,14,20,21].”
From Polymer Pellet Fabrication for Accurate THz-TDS Measurements (2022) · cites this paper as [9]
THz-TDS provides a porosity measure that reflects total void space including micropores, mesopores, and macropores.
“One of the exceptions in the category of the matrix sensitive techniques is THz-TDS, which provides a porosity measure that reflects the total void space including micropores (<2 nm), mesopores (2–50 nm), and macropores (>50 nm) [7].”
From Measuring Open Porosity of Porous Materials Using THz-TDS and an Index-Matching Medium (2020) · cites this paper as [7]
Open porosity is crucial for enabling fluid access and initiating tablet dissolution.
“The open porosity, i.e., the pore space accessible from the surface, is crucial for enabling fluid access and initiating tablet dissolution, which is an essential process in an effective treatment using an orally delivered drug product.”
From Measuring Open Porosity of Porous Materials Using THz-TDS and an Index-Matching Medium (2020) · cites this paper as [7]
Disintegration time is known to largely depend on tablet porosity and is in many cases the rate-determining process.
“DT is known to largely dependent on the tablet porosity and it is in many cases the rate-determining process [6,7].”
From Measuring Open Porosity of Porous Materials Using THz-TDS and an Index-Matching Medium (2020) · cites this paper as [7]
Mercury and helium porosimetry, the usual porosity techniques, take considerable time and damage the sample.
“This may be due partly to the relatively time-consuming and destructive nature of existing conventional porosity measurement methods like mercury or helium porosimetry 16,29,30 .”
From A Fast and Non-destructive Terahertz Dissolution Assay for Immediate Release Tablets (2021) · cites this paper as [16]
Porosity is a dependable and essential quality attribute for tablets, and it governs the mass transport processes behind disintegration and dissolution.
“Tablet porosity is a reliable and fundamental critical quality attribute which controls key mass transport mechanisms that govern disintegration and dissolution behaviour.”
From A Fast and Non-destructive Terahertz Dissolution Assay for Immediate Release Tablets (2021) · cites this paper as [16]
A reason reliable dissolution prediction is hard is that earlier techniques do not directly measure bulk tablet properties like porosity, which control mass transport during disintegration and release.
“This is due to the inability of these methods to directly probe and quantify the bulk physical properties of tablets, e.g.porosity, that directly govern mass transport mechanisms in a tablet during its disintegration and subsequent drug release 16,17 .”
From A Fast and Non-destructive Terahertz Dissolution Assay for Immediate Release Tablets (2021) · cites this paper as [16]
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References 231 · Cited by 154
Research works printed but not linked: 3
- Dullien, F.A.L., 1992. Porous Media, Second. ed. Academic Press Inc.
- Levitt, M.H., 2008. Spin Dynamics, Second Edition. ed. John Wiley & Sons.
- Sheikhveisi, H., 2015. A Function-Based Image Binarization based on Histogram. International Research Journal of Applied and Basic Sciences 9, 418-426.
- Authors
- Markl, D., Strobel, A., Schlossnikl, R., Bøtker, J., Bawuah, P., Ridgway, C., Rantanen, J., Rades, T., Gane, P., Peiponen, K.-E., & Zeitler, J. A.
- Affiliations
- University of Cambridge (GB)
- University of Eastern Finland (FI)
- Omya (Switzerland) (CH)
- University of Copenhagen (DK)
- Corresponding author
- Markl, Daniel
- Venue
- International Journal of Pharmaceutics
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 538
- Issue
- 1-2
- Pages
- 188-214
- ISSN
- 0378-5173 (ISSN-L)
- OpenAlex
- W2784237600
- Cited by
- 154
- References
- 231
- Citations by year
- 2026: 19 · 2025: 23 · 2024: 19 · 2023: 20 · 2022: 13 · 2021: 15 · 2020: 23 · 2019: 14 · 2018: 8
- FWCI
- 1.31
- Type
- journal article
- Language
- en
- Open access
- green
- erepo.uef.fi
- Licence
- cc-by-nc-nd
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- Locations
- International Journal of Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- UEF eRepo (University of Eastern Finland) (submittedVersion, cc-by-nc-nd)
- Strathprints: The University of Strathclyde institutional repository (University of Strathclyde) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Danish Council for Independent Research
- Technology and Production Sciences
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Physical Sciences › Engineering › Computational Mechanics › Granular flow and fluidized beds
- Physical Sciences › Materials Science › Materials Chemistry › Crystallization and Solubility Studies
- Keywords
- tablet microstructure, compaction, porosity, tortuosity, pore connectivity, pore shape, fluid intake, dissolution, solid dosage forms, helium pycnometry, mercury intrusion porosimetry, terahertz time-domain spectroscopy, X-ray computed microtomography, nuclear magnetic resonance, additive manufacturing, drug delivery
- MeSH terms
- Chemistry, Pharmaceutical, Magnetic Resonance Spectroscopy, Tablets, Technology, Pharmaceutical, Porosity, Drug Delivery Systems, Terahertz Spectroscopy, X-Ray Microtomography
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