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Simultaneous investigation of the liquid transport and swelling performance during tablet disintegration.

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Al-Sharabi, Mohammed 
Markl, Daniel 
Mudley, Theona 
Karttunen, Anssi-Pekka 


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.



Disintegration, Liquid transport, Microstructure, Pharmaceutical tablets, Porous media, Swelling, Terahertz, Acetaminophen, Calcium Carbonate, Cellulose, Chemistry, Pharmaceutical, Dose-Response Relationship, Drug, Excipients, Humans, Kinetics, Porosity, Tablets, Terahertz Spectroscopy, Theophylline

Journal Title

Int J Pharm

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Elsevier BV
EPSRC (1943009)
Engineering and Physical Sciences Research Council (EP/P006965/1)
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