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

Abstract

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.

Characterisation of pore structures of pharmaceutical tablets: A review

“…These disk-shaped blocks are described by the factor I that represents their radius to thickness ratio. The model was also shown to describe the relationship very well between porosity and tortuosity for functionalised calcium carbonate (FCC) tablets (Markl et al, 2018b). Wu et al, 2006 determined the fastest route through the pore space of sodium chloride compacts by analysing crosssections of the tablets using SEM.…”

“…This < = parameter revealed that material attributes, such as particle size or granule density, strongly impact the anisotropy of the pore structure. The degree of anisotropy particularly influences the tortuosity and constrictivity of the structure and eventually the disintegration performance of the tablet (Markl et al, 2018b).…”

“…It has been demonstrated for porous media (Cai and Yu, 2011;Dullien, 1992) in general but also for pharmaceutical tablets (Markl et al, 2018b) that the tortuosity, connectivity, as well as pore shape, size and orientation affect the liquid imbibition process (Figure 1). To advance the understanding of the relationship between the manufacturing process and the performance of the final drug product, it is essential to quantitatively measure, and to routinely report, these characteristic pore parameters in a tablet in addition to the commonly used descriptor of tablets, namely total porosity or solid fraction.…”

Investigating elastic relaxation effects on the optical properties of functionalised calcium carbonate compacts using optics-based Heckel analysis

“…The change in the effective refractive index and porosity clearly indicates the influence of elastic relaxation on the pore structure. This will in turn impact the liquid uptake rate that is part of the disintegration process of pharmaceutical tablets (Markl et al, 2018b). This post-compaction variation of the pore structure will also directly affect the dissolution performance.…”

Loading of Porous Functionalized Calcium Carbonate Microparticles: Distribution Analysis with Focused Ion Beam Electron Microscopy and Mercury Porosimetry

“…Markl et al used a combination of terahertz pulse imaging, µCT, MIP and pycnometry together with an experimental setting for water sorption of FCC compacts. They interpreted the results as anisotropic pores that are perpendicular to the compaction direction of a tablet [30,31]. However, so far, no convincing data has been available which reveals the internal structure of single FCC particles.…”