(M0930-09-60) Terahertz Pulsed Imaging (TPI) Based Liquid Transport Profiling For the Tablet Disintegration Process Analysis

Purpose: The disintegration process of pharmaceutical tablets refers to the physical fragmentation of an intact tablet into smaller particles, aiming to enhance the contact between the drug substance and the dissolution medium. This process is particularly crucial for immediate-release tablets to ensure their bioavailability and efficacy [1]. While the widely adopted USP < 701 > test method provides a standard procedure for quantifying the disintegration process, it offers limited scientific and mechanistic insights. This study aims to develop a more scientific investigation method on the disintegration process so that the acquired information can be utilised for the process analysis.

Methods: Previous studies have successfully extracted the displacement of the liquid-front in the tablet matrix in-situ using terahertz pulsed imaging technique [2,3]. However, the measurement setup required a specific sample geometry to match the flow cell sample holder, thereby limiting the samples in shape, size and thickness to a range which did not suit most commercial tablets. In this study, we developed and employed a novel experimental setup for liquid transport profiling of tablets of arbitrary shape. The setup includes a bespoke sample holder that exposes over half of the tablet surface to the dissolution medium, allowing immersion of the exposed tablet surface [4]. Experimental materials consisted of five batches of complex formulation placebo tablets, which were tableted using a compaction simulator at five target compaction pressures ranging from 50 MPa to 250 MPa.

Results: The acquired liquid transport profiles revealed strong correlation between the tablet porosity and the rate of water uptake: as the compaction pressure increased, the rate of water uptake decreased. Additionally, two regimes of water uptake were observed from the profiles: a rapid uptake regime at the beginning of the imbibition and a predominantly linear regime thereafter. A comparison between the disintegration time and the water uptake time indicated that the tablets with quick disintegration (i.e. less than 30 seconds) had shorter water uptake times, while the opposite trend was observed for slow-disintegrating samples.

Conclusion: This study presents a novel terahertz liquid ingress investigation method that enables the extraction of liquid transport profiles from tablets with different porosity tablets, providing insights into how the dissolution medium is imbibed during the disintegration process. These profiles can be utilised for analysing liquid transport kinetics and developing a mechanistic model of the disintegration process.

References: [1] Markl D. and Zeitler J.A. Pharm Res 34. 5 (2017)
[2] Yassin, S. et al, J Pharm Sci 104, 3449-3450 (2015)
[3] Al-Sharabi, M. et al. Chem Eng Res 165, 386-397 (2021)
[4] Lee J. et al, Int J. Pharm 635, 122726 (2023)

Terahertz pulsed imaging (TPI) based liquid transport measurement setup for pharmaceutical tablet disintegration analysis

Using a novel terahertz liquid transport investigation method, advancing liquid front in up to 5.7 mm thick tablet were successfully monitored without prior modification of the samples.