Crosslinking-Driven Enhancement of HPMC Films for Ocular Delivery: <i>In-Vitro</i> Characterization of Diclofenac Release

Polymer crosslinking plays a critical role in controlling drug release, enhancing ocular film stability, and improving mechanical properties. This study developed sustained-release ocular films using HPMC K15 crosslinked with citric acid (CA) via esterification, incorporating diclofenac as a model NSAID. Four formulations (DF1–DF4) were prepared with increasing CA ratios (0, 1:0.1, 1:0.3, and 1:0.5). FTIR confirmed ester bond formation, DSC indicated enhanced thermal behavior, and NMR verified structural modifications. Film thickness ranged from 0.156 ± 0.02 mm to 0.165 ± 0.032 mm, with a surface pH between 6.38 and 7.13. All formulations exhibited high drug content (>95%), with DF3 achieving 99.4 ± 0.8%. Moisture uptake ranged from 16.57 ± 0.5% (DF4) to 24.12 ± 0.43% (DF3). DF3 had the highest swelling (590± 25%) and erosion, while DF4 had the lowest (330 ± 25%). XRD confirmed diclofenac amorphization, and SEM showed uniform dispersion. DF3 exhibited maximum in vitro release (104.5 ± 4.2% at, 90 min), following Higuchi kinetics (R2 = 0.99) and Fickian diffusion (n = 0.48). Ex vivo permeation in DF3 reached 98.2 ± 5.1% at 24 h. DPPH assay revealed >70% antioxidant activity, and stability studies confirmed >99% drug retention after 3 months.