Fast and non-destructive pore structure analysis using terahertz time-domain spectroscopy

Daniel Markl, Prince Bawuah, Cathy Ridgway, Sander van den Ban, Daniel J. Goodwin, Jarkko Ketolainen, Patrick Gane, Kai Erik Peiponen, J. Axel Zeitler

Research output: Contribution to journalArticle

13 Citations (Scopus)
13 Downloads (Pure)

Abstract

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, Sa, to describe the anisotropy in pore structure of pharmaceutical tablets based on terahertz time-domain spectroscopy measurements. The Sa 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 Sa 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.

Original languageEnglish
Pages (from-to)102-110
Number of pages9
JournalInternational Journal of Pharmaceutics
Volume537
Issue number1-2
Early online date13 Dec 2017
DOIs
Publication statusPublished - 15 Feb 2018

Keywords

  • anisotropy
  • disintegration
  • microstructure
  • pharmaceutical tablet
  • pore structure
  • terahertz

Fingerprint Dive into the research topics of 'Fast and non-destructive pore structure analysis using terahertz time-domain spectroscopy'. Together they form a unique fingerprint.

  • Cite this

    Markl, D., Bawuah, P., Ridgway, C., van den Ban, S., Goodwin, D. J., Ketolainen, J., ... Zeitler, J. A. (2018). Fast and non-destructive pore structure analysis using terahertz time-domain spectroscopy. International Journal of Pharmaceutics, 537(1-2), 102-110. https://doi.org/10.1016/j.ijpharm.2017.12.029