Terahertz pulsed imaging as a new method for investigating the liquid transport kinetics of α-alumina powder compacts

Al-Sharabi, Mohammed; Markl, Daniel; Vivacqua, Vincenzino; Bawuah, Prince; Maclean, Natalie; Bentley, Marian; York, Andrew P. E.; Marigo, Michele; Huang, Karen; Zeitler, J. Axel

doi:10.1016/j.cherd.2020.11.006

Cited by 11 publications

(4 citation statements)

References 52 publications

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“…The liquid penetration and tablet swelling were measured using a commercial terahertz-pulsed imaging system (TPI, TeraPulse 4000, Teraview Ltd., Cambridge, UK) in combination with a bespoke flow cell [ 33 ]. The TPI was set up with a fibre-based reflection probe equipped with an 18 mm focal-length silicon lens.…”

Section: Methodsmentioning

confidence: 99%

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Modelling the Evolution of Pore Structure during the Disintegration of Pharmaceutical Tablets

et al. 2023

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Pharmaceutical tablet disintegration is a critical process for dissolving and enabling the absorption of the drug substance into the blood stream. The tablet disintegration process consists of multiple connected and interdependent mechanisms: liquid penetration, swelling, dissolution, and break-up. One key dependence is the dynamic change of the pore space in a tablet caused by the swelling of particles while the tablet takes up liquid. This study analysed the changes in the pore structure during disintegration by coupling the discrete element method (DEM) with a single-particle swelling model and experimental liquid penetration data from terahertz-pulsed imaging (TPI). The coupled model is demonstrated and validated for pure microcrystalline cellulose (MCC) tablets across three porosities (10, 15, and 22%) and MCC with three different concentrations of croscarmellose sodium (CCS) (2, 5, and 8% w/w). The model was validated using experimental tablet swelling from TPI. The model captured the difference in the swelling behaviour of tablets with different porosities and formulations well. Both the experimental and modelling results showed that the swelling was lowest (i.e., time to reach the maximum normalised swelling capacity) for tablets with the highest CCS concentration, cCCS = 8%. The simulations revealed that this was caused by the closure of the pores in both the wetted volume and dry volume of the tablet. The closure of the pores hinders the liquid from accessing other particles and slows down the overall swelling process. This study provides new insights into the changes in the pore space during disintegration, which is crucial to better understand the impact of porosity and formulations on the performance of tablets.

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Section: Methodsmentioning

confidence: 99%

“…Since the flow cell was not included in the DEM simulation ( Figure 1 b), only the front face swelling was recorded in the simulation. More details about the flow cell and its design can be foundin [ 33 ].…”

Section: Methodsmentioning

confidence: 99%

Modelling the Evolution of Pore Structure during the Disintegration of Pharmaceutical Tablets

et al. 2023

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“…As a result, one reflection waveform per second was generated. A schematic of the experimental setup is shown in Figure A1 in the Appendix A and further detail was reported previously [ 15 ]. The fundamental principle of data acquisition and data processing of this method has been explained in detail in previous studies [ 16 , 17 ].…”

Section: Methodsmentioning

confidence: 99%

“…In this cell the tablet is held horizontally in a fixed position and is exposed to a laminar flow of dissolution medium at constant velocity at its lower face. Terahertz time-domain reflection measurements are performed through the dry upper face of the tablet [ 15 ]. The use of the flow cell setup makes it possible to separate the wicking process of dissolution medium into the tablet from shear erosion under turbulent flow conditions.…”

Section: Introductionmentioning

confidence: 99%

Insights into the Control of Drug Release from Complex Immediate Release Formulations

et al. 2021

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The kinetics of water transport into tablets, and how it can be controlled by the formulation as well as the tablet microstructure, are of central importance in order to design and control the dissolution and drug release process, especially for immediate release tablets. This research employed terahertz pulsed imaging to measure the process of water penetrating through tablets using a flow cell. Tablets were prepared over a range of porosity between 10% to 20%. The formulations consist of two drugs (MK-8408: ruzasvir as a spray dried intermediate, and MK-3682: uprifosbuvir as a crystalline drug substance) and NaCl (0% to 20%) at varying levels of concentrations as well as other excipients. A power-law model is found to fit the liquid penetration exceptionally well (average R2>0.995). For each formulation, the rate of water penetration, extent of swelling and the USP dissolution rate were compared. A factorial analysis then revealed that the tablet porosity was the dominating factor for both liquid penetration and dissolution. NaCl more significantly influenced liquid penetration due to osmotic driving force as well as gelling suppression, but there appears to be little difference when NaCl loading in the formulation increases from 5% to 10%. The level of spray dried intermediate was observed to further limit the release of API in dissolution.

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Analytical Characterisation of 3D‐Printed Medicines

Lima,

Sá‐Barreto,

Cunha‐Filho

2024

3D Printing of Pharmaceutical and Drug Delivery Devices

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Terahertz pulsed imaging as a new method for investigating the liquid transport kinetics of α-alumina powder compacts

Cited by 11 publications

References 52 publications

Modelling the Evolution of Pore Structure during the Disintegration of Pharmaceutical Tablets

Modelling the Evolution of Pore Structure during the Disintegration of Pharmaceutical Tablets

Insights into the Control of Drug Release from Complex Immediate Release Formulations

Analytical Characterisation of 3D‐Printed Medicines

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