Characterisation of the Pore Structure of Functionalised Calcium Carbonate Tablets by Terahertz Time-Domain Spectroscopy and X-ray Computed Microtomography

Abstract

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 functionalised calcium carbonate (FCC), which enables the manufacture of compacts with a bimodal pore size distribution consisting of larger inter-particle and fine intra-particle pores. Five sets of FCC tablets with a target porosity of 45% to 65% were prepared in 5% steps and characterised using terahertz time-domain spectroscopy (THz-TDS) and X- ray computed microtomography (XμCT). THz-TDS was employed to derive the porosity using effective medium approximations (EMAs), i.e., the traditional and an anisotropic Bruggeman model. The anisotropic Bruggeman model yields the better correlation with the nominal porosity (R2 = 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 behaviour of the dielectric porous medium. The results from XμCT confirmed the non-spherical shape as well as the orientation of the pores and it further revealed that the anisotropic behaviour is mainly caused by the inter-particle pores. The information from both techniques provide 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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Characterisation of the Pore Structure of Functionalised Calcium Carbonate Tablets by Terahertz Time-Domain Spectroscopy and X-ray Computed Microtomography
Markl D, Wang P, Ridgway C, Karttunen AP, Chakraborty M, Bawuah P, Pääkkönen P, Gane P, Ketolainen J, Peiponen K, Zeitler JA, Characterisation of the Pore Structure of Functionalised Calcium Carbonate Tablets by Terahertz Time-Domain Spectroscopy and X-ray Computed Microtomography, Journal of Pharmaceutical Sciences (2017), doi: 10.1016/ j.xphs.2017.02.028.
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