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

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.

A Fast and Non-destructive Terahertz Dissolution Assay for Immediate Release Tablets

“…4 and 5). In as much as the current analyses place much emphases on the influence of porosity, we are very much aware of the significant role played by other factors such as hydrophilicity (contact angle), wetting time and water absorption ratio on the dissolution/disintegration time of especially orodispersible tablets (ODTs) 26,47,48 . It should be clarified at this point that, although the dissolution behaviour of a given drug substance significantly depends on its solubility properties, the rate at which the tablet disintegrates also plays a significant role by exposing the drug particles to the dissolution medium.…”

Exploring the performance-controlling tablet disintegration mechanisms for direct compression formulations

“…As a result, several groups have applied novel approaches such as magnetic resonance imaging (Quodbach et al, 2014a,b;Dvořák et al, 2020), broadband acoustic resonance dissolution spectroscopy (BARDS) (O'Mahoney et al, 2020), image analysis (Berardi et al, 2018) and stress relaxation measurements (Tomas et al, 2018) which can be used to study the underlying processes occurring during disintegration and dissolution. Similarly, terahertz pulsed imaging (TPI) has been used to study liquid penetration in and swelling of powder compacts (Yassin et al, 2015;Al-Sharabi et al, 2020). The test conditions have also been shown to influence the disintegration and dissolution rates.…”

Controlled Drug Release by the Pore Structure in Polydimethylsiloxane Transdermal Patches

“…Relevance of the material porosity for water permeation and controlled drug release was often taken into consideration when different dosage forms were characterized. Maximizing the permeability for water with retained mechanical durability is usually the goal in development of fast disintegrating tablets or extended-release coated tablets [12][13][14]. More sophisticated control of the drug release is usually expected for microspheres, implants or hydrogels, where swelling additionally contributes to the diffusion mechanism [15][16][17].…”