A multidimensional strategy combining surface science, release kinetics, and morphology to guide sustained-release tablet development

: This study investigates the relationship between surface thermodynamic properties and drug release kinetics in galantamine–HPMC compressed matrices. An integrated experimental strategy was applied, encompassing excipient compatibility (FTIR, DSC), particle and flow characterization, surface energy analysis (contact angle, OWRK model), kinetic modeling, and morphological documentation (SEM, real-time imaging). FTIR and DSC confirmed molecular dispersion and absence of incompatibilities. The matrix exhibited intermediate wettability (θ = 71.83°, SFET = 31.58 mJ/m 2 ), influencing hydration and gel formation. Drug release followed a triphasic mechanism—latency, active diffusion, and erosion—best described by heuristic models, particularly the Gompertz model (R 2 = 0.9984), with similarly high fits for the Weibull, Logistic, and modified Hill models (R 2 ≥ 0.997). SEM and macroscopic imaging revealed progressive structural evolution, validating the proposed release dynamics. These findings demonstrate that surface attributes critically modulate hydration and drug transport, offering rational design criteria for modified-release oral systems. Studies integrating spectroscopic, thermodynamic, kinetic, and morphological dimensions remain scarce, highlighting the relevance and novelty of this approach.