1. Simultaneous investigation of the liquid transport and swelling performance during tablet disintegration
- Author
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J. Axel Zeitler, Theona Mudley, Jarkko Ketolainen, Kai-Erik Peiponen, Mohammed Al-Sharabi, Cathy J. Ridgway, Thomas Rades, Daniel Markl, Prince Bawuah, Patrick A.C. Gane, Anssi-Pekka Karttunen, Bawuah, Prince [0000-0001-7688-0065], Zeitler, Axel [0000-0002-4958-0582], Apollo - University of Cambridge Repository, University of Cambridge, University of Strathclyde, University of Eastern Finland, Omya AG, Department of Bioproducts and Biosystems, University of Copenhagen, Aalto-yliopisto, and Aalto University
- Subjects
Chemistry, Pharmaceutical ,Terahertz ,Compaction ,Pharmaceutical Science ,02 engineering and technology ,030226 pharmacology & pharmacy ,chemistry.chemical_compound ,0302 clinical medicine ,WATER ,Disintegration ,POWDERED PREPARATIONS ,Microstructure ,Dissolution ,Liquid transport ,Pharmaceutical tablets ,TASTE-MASKING ,021001 nanoscience & nanotechnology ,TIME ,Microcrystalline cellulose ,MICROCRYSTALLINE CELLULOSE ,Drug delivery ,Swelling ,medicine.symptom ,0210 nano-technology ,Porosity ,Tablets ,RM ,Materials science ,Porous media ,Calcium Carbonate ,PORE STRUCTURE ,Excipients ,03 medical and health sciences ,Theophylline ,medicine ,Humans ,Cellulose ,Acetaminophen ,Terahertz Spectroscopy ,Dose-Response Relationship, Drug ,POROSITY ,DIRECT COMPRESSION ,Kinetics ,chemistry ,Chemical engineering ,PHARMACEUTICAL TABLETS ,IMMEDIATE-RELEASE ,Porous medium - Abstract
Fast disintegrating tablets have commonly been used for fast oral drug delivery to patients with swallowing difficulties. The different characteristics of the pore structure of such formulations influence the liquid transport through the tablet and hence affect the disintegration time and the release of the drug in the body. In this work, terahertz time-domain spectroscopy and terahertz pulsed imaging were used as promising analytical techniques to quantitatively analyse the impact of the structural properties on the liquid uptake and swelling rates upon contact with the dissolution medium. Both the impact of porosity and formulation were investigated for theophylline and paracetamol based tablets. The drug substances were either formulated with functionalised calcium carbonate (FCC) with porosities of 45% and 60% or with microcrystalline cellulose (MCC) with porosities of 10% and 25%. The terahertz results reveal that the rate of liquid uptake is clearly influenced by the porosity of the tablets with a faster liquid transport observed for tablets with higher porosity, indicating that the samples exhibit structural similarity in respect to pore connectivity and pore size distribution characteristics in respect to permeability. The swelling of the FCC based tablets is fully controlled by the amount of disintegrant, whereas the liquid uptake is driven by the FCC material and the interparticle pores created during compaction. The MCC based formulations are more complex as the MCC significantly contributes to the overall tablet swelling. An increase in swelling with increasing porosity is observed in these tablets, which indicates that such formulations are performance-limited by their ability to take up liquid. Investigating the effect of the microstructure characteristics on the liquid transport and swelling kinetics is of great importance for reaching the next level of understanding of the drug delivery, and, depending on the surface nature of the pore carrier function, in turn controlling the performance of the drug mainly in respect to dissolution in the body.
- Published
- 2020
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