Multiscale characterization and physically based modelling reveal how structural gradients govern release in hydrogel matrix patch systems

Hydrogel patches based on alginate and gelatin were fabricated in four formulations (PS0, PS1, PS0C, PS1C) to elucidate how morphology, thermal stability, optical response, and swelling behaviour jointly determine their suitability as drug-release platforms. A comprehensive multi-technique characterization was performed, integrating atomic force microscopy (AFM), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), optical reflectance/transmittance spectroscopy, profilometry, and swelling kinetics. AFM revealed that non-crosslinked samples (PS0, PS1) exhibit smooth but mechanically fragile surfaces, whereas calcium crosslinking (PS0C, PS1C) induces a marked increase in nanoscale heterogeneity and load-bearing microdomains. Thermal analyses (TGA/DSC) confirmed the structural reinforcement of crosslinked networks, showing higher transition temperatures, reduced mass-loss rates, and increased residual mass fractions. Optical measurements demonstrated that crosslinking and dye loading modulate internal scattering and absorption, reflecting changes in microstructural organization. Swelling experiments further highlighted the dominant role of ionic crosslinking in controlling water uptake, with PS0 and PS1 undergoing rapid destabilization, while PS0C and PS1C maintain structural integrity and exhibit slower, diffusion-limited hydration. Taken together, these results show that the combined morphological, thermal, optical, and swelling signatures provide a coherent physical basis for modelling internal diffusivity in Alg/Gel hydrogels. The observed structure–property relationships establish the mechanistic foundation required to predict and optimize drug release from these patches in realistic application scenarios.