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.

Cost effectiveness, ease of use and patient compliance make pharmaceutical tablets the most popular and widespread form to administer a drug to a patient. Tablets typically consist of an active pharmaceutical ingredient and a selection from various excipients. A novel highly porous excipient, functionalised calcium carbonate (FCC), was designed to facilitate rapid liquid uptake leading to disintegration times of FCC based tablets in the matter of seconds. Five sets of FCC tablets with a target porosity of 45-65% in 5% steps were prepared and characterised using terahertz pulsed imaging (TPI). The high acquisition rate (15 Hz) of TPI enabled the analysis of the rapid liquid imbibition of water into these powder compacts. The penetration depth determined from the TPI measurements as a function of time was analysed by the power law and modelled for both the inertial (initial phase) and Lucas-Washburn (LW, longer time Laplace-Poiseuillian) regimes. The analysis of the hydraulic radius estimated by fitting the liquid imbibition data to the LW equation demonstrates the impact of the porosity as well as the tortuosity of the pore channels on the liquid uptake performance. The tortuosity was related to the porosity by a geometrical model, which shows that the powder compact is constructed by aggregated particles with low permeability and its principal axis perpendicular to the compaction direction. The consideration of the tortuosity yielded a very high correlation (R 2 = 0.96) between the porosity and the hydraulic pore radius. The terahertz data also resolved fluctuations (0.9-1.3 Hz) of the liquid movement which become more pronounced and higher in frequency with increasing porosity, which is attributed to the constrictivity of pore channels. This study highlights the strong impact of a tablet's microstructure on its liquid penetration kinetics and thus on its disintegration behaviour.

Terahertz pulsed imaging (TPI) is used to characterise microstructural changes during the hydration of pharmaceutical tablets. In particular, terahertz reflection measurements provide quantitative information about the liquid penetration, swelling and the formation of cracks. X-ray computed microtomography (XµCT) is employed to characterise the microstructure of the dry powder compact in terms of porosity, equivalent volume diameter and length of the pores. Both XµCT and TPI can provide valuable information about the impact of the microstructure on the performance of drugs.