Characterization of the Pore Structure of Functionalized 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 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 = 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.

Resolving the rapid water absorption of porous functionalised calcium carbonate powder compacts by terahertz pulsed imaging

“…Since X CT and THz-TDS are non-destructive techniques, the tablets were still intact after the measurement and were used in this study. This facilitates the direct correlation of the results from this study with that from Markl et al (2017b). In general, FCC is formed in a process whereby the surface of micrometre sized calcium carbonate particles is etched and then re-precipitated to create a highly porous, high surface area material.…”

“…The diameter and thickness of the tablets were kept constant at 10 mm and 1.5 mm, respectively, by varying the material weight. The pore structure of these FCC tablets was characterised by Markl et al (2017b) using mercury porosimetry, X CT and THz-TDS. Since X CT and THz-TDS are non-destructive techniques, the tablets were still intact after the measurement and were used in this study.…”

“…3). Since the intra-particle pore structure of the FCC particles is similar between the different batches (Markl et al, 2017b), the variations in liquid uptake kinetics of the different batches are primarily affected by the inter-particle pore architecture which was formed during powder compaction. The absorption behaviour depends on the pore size distribution and the pore connectivity amongst other factors such as pore network geometry and surface energy.…”

“…A highly viable excipient for ODT formulations is functionalised calcium carbonate (FCC), which has a high intra-particle porosity (Stirnimann et al, 2013). FCC based tablets have a discretely separable bimodal pore size distribution, consisting of large inter-particle and fine intra-particle pores (Markl et al, 2017b). The inter-particle pores are formed during the powder compaction and therefore, they can be modified by adjusting the compaction process.…”

“…The insitu monitoring approach by means of terahertz technology was further developed to study the rapid imbibition of the FCC tablets. The imbibition process was analysed and modelled on the basis of the TPI data and it was related to the pore structure properties of the same tablets determined by THz-TDS (Markl et al, 2017b).…”