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Activation of Release by Hydration in Pharmaceutical Tablets Studied by Terahertz Pulsed Imaging



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Dong, Runqiao 


Tablets are one of the most common pharmaceutical dosage forms. The liquid ingress into a tablet is considered to be the first, and often rate-determining, step for tablet disintegration and subsequent drug dissolution. Even for tablets that do not disintegrate (e.g. sustained release tablets), hydration of the oral solid dosage form still plays a critical role in activating the drug release. In this thesis, terahertz pulsed imaging (TPI) was used to investigate the hydration kinetics of pharmaceutical tablets in a one-dimensional liquid penetration setup. The capability of terahertz pulses to probe through, and respond to, interfaces of different structures inside a tablet and the high data acquisition rate of TPI makes it a highly suitable tool for this study.

The TPI method was first demonstrated on uncoated tablets. The kinetics of liquid penetration extracted from TPI data was compared to the corresponding dissolution testing results, and the mechanistic impact of various key ingredients in the formulation was revealed. The research then focused on coated tablets where the presence of the layered structure stepped up the complexity of the hydration process. The tablet cores were made of pure microcrystalline cellulose (MCC) and a PVA-based (polyvinyl alcohol) immediate-release coating formulation was applied in the first step. Initially, vacuum compression moulding was used to apply the coating layer. Although the coatings prepared by this method were highly porous and lacked uniformity, TPI managed to quantitatively resolve multiple stages of liquid transport through coating and tablet core, and identify a discontinuity in liquid transport at the coating-core interface in contrast to the uncoated tablets. Subsequently, a spraying system was employed to apply film coating of industrial quality. Similar multi-staged liquid transport behaviour was consistently observed and a systematic approach for data processing was developed. A multiple linear regression method was used to analyse the dependency of the hydration kinetics of coating and core layer on both coating thickness (30 μm to 250 μm) and core porosity (10% to 30%). Finally, a EC-based (ethyl cellulose) sustained-release coating was studied. The slow water ingress was characterised by the amount of swelling in core monitored by TPI instead of directly tracing the water front. Various conditions triggered in a prolonged hydration process such as crack formation were identified.

The subtle details of liquid penetration captured uniquely by TPI provide valuable insights into the physical steps involved in drug release upon hydration from tablets. With suitable complementary tools, TPI presents great potential for developing better understanding to aid the rational design of pharmaceutical formulations and processes.





Zeitler, Jochen


Film Coatings, Pharmaceutical Tablets, Terahertz Pulsed Imaging, Terahertz Time-Domain Spectroscopy


Doctor of Philosophy (PhD)

Awarding Institution

University of Cambridge