A smart ingestible capsule for real-time monitoring of stimuli-responsive polymer dissolution kinetics and oral drug release in the gastrointestinal tract.

Oral drug delivery relies on precise, site-specific release within the gastrointestinal (GI) tract, commonly achieved using stimuli-responsive polymer (SRP) coatings that regulate dissolution under varying physiological conditions to maximize therapeutic efficacy. Continuous advancements in polymer chemistry and composite formulations have enabled increasingly sophisticated control over drug release profiles. However, a critical challenge remains in accurately assessing how these materials degrade, dissolve, and perform under true in vivo GI conditions. While numerous in vitro models have been developed to approximate physiological environments, they often fail to capture the complexity of GI dynamics, including variations in pH, fluid composition, motility, and transit behavior. As a result, there is a significant need for technologies capable of directly monitoring the real-time behavior of these materials during in vivo transit to better understand their performance and guide formulation design. To address this unmet need, we present a miniaturized ingestible sensing capsule designed for in situ, formulation-centric evaluation of polymer dissolution dynamics within the GI tract. The platform integrates impedance-based sensing to monitor changes in the physical and structural integrity of SRP coatings and polymeric pharmaceutical formulations during dissolution, alongside potentiometric pH sensing for anatomical localization within the GI environment. This dual-sensing approach enables simultaneous tracking of material degradation and spatial positioning, providing direct insight into where and how dissolution occurs in vivo. Systematic in vitro characterization using simulated and extracted GI fluids across physiologically relevant conditions demonstrated an approximately 100-fold reduction in impedance upon dissolution of the polymeric coating, reflecting sensitivity to structural breakdown and fluid ingress. The integrated pH sensor exhibited a linear response across the physiologically relevant range of pH 2 to 8, enabling reliable identification of GI segments. A power-optimized hardware-software co-design enabled periodic sensing and wireless data transmission at intervals between 250 ms and 1 s, achieving an average power consumption as low as 90.7 μW. This low-power operation supports extended device functionality over time scales exceeding typical GI transit durations, while maintaining stable performance and minimizing battery-related risks. As a proof of concept, the system was evaluated using widely used pH-responsive SRP coatings, including Eudragit® EPO (gastric-targeted dissolution) and Eudragit® L100 (intestinal-targeted dissolution). Device performance was validated through both in vitro studies and in vivo evaluation in a porcine model under endoscopy-guided placement, demonstrating accurate tracking of coating dissolution kinetics with spatial correlation to GI segments. Drug release profiles were independently confirmed using spectrometric quantification of identically coated commercial pharmaceutical tablets, establishing consistency between electrical sensing outputs and pharmacological release behavior. Overall, this ingestible platform enables quantitative, spatially resolved, in vivo assessment of polymer-based drug delivery systems, providing a powerful tool for researchers and pharmaceutical developers to directly evaluate formulation performance under realistic physiological conditions. The technology is envisioned to support the design, optimization, and clinical translation of advanced oral drug delivery systems by enabling improved understanding of material behavior, release kinetics, and patient-specific variability in the GI tract.