Pore network within tablets structurally regulates sustained drug release from insoluble matrix tablets

Matrix tablets, a basic type of controlled and sustained-release formulations, are widely used whilst their dynamic microstructure evolution in the release phase remains insufficiently investigated. In this study, synchrotron radiation X-ray microtomography (SR-μCT) and pore network analysis were used to resolve the spatial distribution of potassium chloride (KCl) within tablets and investigate the structure-transport relationship. The results demonstrate that pore networks originate from the spatial distribution of drug crystals rather than being randomly generated, establishing a direct link between initial formulation structure and subsequent transport pathways. Isolated pore domains act as transient drug reservoirs and progressively integrate into a percolating network that enables long-range transport. Although the effective diffusion distance increases during dissolution, enhanced network connectivity and transport area compensate for the increased transport resistance. The membrane maintains structural integrity throughout the process. This study provides microstructure-resolved insight into how pore network evolution governs drug release. The structural diffusion index (SDI) is introduced as a structure-dependent descriptor to characterize pore network evolution. Overall, this work advances the understanding of sustained-release mechanisms and offers a framework for the rational design of sustained-release formulations through pore network regulation.