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.

PurposeA 3D printer was used to realise compartmental dosage forms containing multiple active pharmaceutical ingredient (API) formulations. This work demonstrates the microstructural characterisation of 3D printed solid dosage forms using X-ray computed microtomography (XμCT) and terahertz pulsed imaging (TPI).MethodsPrinting was performed with either polyvinyl alcohol (PVA) or polylactic acid (PLA). The structures were examined by XμCT and TPI. Liquid self-nanoemulsifying drug delivery system (SNEDDS) formulations containing saquinavir and halofantrine were incorporated into the 3D printed compartmentalised structures and in vitro drug release determined.ResultsA clear difference in terms of pore structure between PVA and PLA prints was observed by extracting the porosity (5.5% for PVA and 0.2% for PLA prints), pore length and pore volume from the XμCT data. The print resolution and accuracy was characterised by XμCT and TPI on the basis of the computer-aided design (CAD) models of the dosage form (compartmentalised PVA structures were 7.5 ± 0.75% larger than designed; n = 3).ConclusionsThe 3D printer can reproduce specific structures very accurately, whereas the 3D prints can deviate from the designed model. The microstructural information extracted by XμCT and TPI will assist to gain a better understanding about the performance of 3D printed dosage forms.Electronic supplementary materialThe online version of this article (doi:10.1007/s11095-016-2083-1) contains supplementary material, which is available to authorized users.

Terahertz (THz) radiation encompasses a wide spectral range within the electromagnetic spectrum that extends from microwaves to the far infrared (100 GHz to ~30 THz). Within its frequency boundaries exist a broad variety of scientific disciplines that have presented, and continue to present, technical challenges to researchers. During the past 50 years, for instance, the demands of the scientific community have substantially evolved and with a need for advanced instrumentation to support radio astronomy, Earth observation, weather forecasting, security imaging, telecommunications, non-destructive device testing and much more. Furthermore, applications have required an emergence of technology from the laboratory environment to production-scale supply and in-the-field deployments ranging from harsh ground-based locations to deep space. In addressing these requirements, the research and development community has advanced related technology and bridged the transition between electronics and photonics that high frequency operation demands. The multidisciplinary nature of THz work was our stimulus for creating the 2017 THz Science and Technology Roadmap (S S Dhillon et al 2017 J. Phys. D: Appl. Phys. 50 043001). As one might envisage, though, there remains much to explore both scientifically and technically and the field has continued to develop and expand rapidly. It is timely, therefore, to revise our previous roadmap and in this 2023 version we both provide an update on key developments in established technical areas that have important scientific and public benefit, and highlight new and emerging areas that show particular promise. The developments that we describe thus span from fundamental scientific research, such as THz astronomy and the emergent area of THz quantum optics, to highly applied and commercially and societally impactful subjects that include 6G THz communications, medical imaging, and climate monitoring and prediction.

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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.