Yasir Qasim Almajidi

Background/Objectives: Rebamipide is a gastroprotective agent with poor aqueous solubility and rapid gastrointestinal clearance, leading to reduced therapeutic efficiency. This study aimed to enhance the solubility, mucoadhesion, and sustained oral delivery of Rebamipide through the development of a deep eutectic mixture (DEM)-based bioadhesive controlled-release granule formulation. Methods: In silico hydrogen-bonding interactions between Rebamipide, malonic acid, and urea were analyzed using CCDC tools. A thermodynamically stable DEM (1:3:1) was prepared and incorporated into bioadhesive granules using chitosan and HPMC. Physicochemical characterization was conducted using FTIR, DSC, TGA, and PXRD. Solubility, in vitro dissolution, ex vivo mucoadhesion (sheep gastric mucosa), and in vivo gastric retention (BaSO₄-loaded granules in rats) were evaluated. Results: The optimized DEM significantly enhanced Rebamipide solubility (10.08 mg/mL vs. 0.045 mg/mL). Solid-state analyses confirmed hydrogen-bond formation and reduced crystallinity. DEM granules exhibited sustained drug release over 24 h (99.7 ± 0.8%) with improved dissolution efficiency compared to the marketed tablet (Mucosta®, 100 mg; T₅₀%: 5.03 h vs. 0.82 h). Kinetic modeling indicated non-Fickian anomalous transport (n = 0.47). The bioadhesive force of DEM granules (0.29 ± 0.02 N) was significantly higher than that of the pure drug and physical mixture. In vivo radiographic studies confirmed prolonged gastric retention. Conclusions: The DEM-based bioadhesive granule system effectively improves solubility, dissolution rate, mucoadhesion, and gastric retention of Rebamipide. This approach represents a promising platform for once-daily gastroretentive oral delivery, pending further pharmacokinetic evaluation.

Diabetic foot ulcers (DFUs) are chronic, hard-to-heal wounds requiring dressings that can address infection, oxidative stress, and impaired tissue regeneration simultaneously. This study aimed to develop chitosan-based thermoresponsive hydrogels co-loaded with repaglinide (Ripa) and difluorinated curcumin (dfCur) and evaluate their physicochemical properties, antibacterial activity, and cytocompatibility. Hydrogels were synthesized using chitosan and β-glycerophosphate, loaded with Ripa (3% w/v), dfCur (1% w/v), or both. Morphology, chemistry, swelling, porosity, degradation, and drug release were characterized using FESEM, ATR-FTIR, gravimetric methods, and UV–Vis spectrophotometry. Cytocompatibility was assessed via MTT assay with NIH3T3 fibroblasts, and antibacterial activity was tested against Staphylococcus aureus and Escherichia coli. Data were analyzed using one-way ANOVA with p < 0.05 considered significant. Dual-drug hydrogels exhibited the highest swelling capacity (~ 115%) and fastest degradation (46–48% mass retained at day 28), with sustained release of both drugs over 7 days. Fibroblast viability was significantly enhanced for dual-drug hydrogels (128.4 ± 3.2%, p < 0.001 vs. control), and antibacterial activity was strongest in dfCur-containing formulations, showing inhibition zones of 21.6 ± 1.4 mm for S. aureus and 19.3 ± 1.2 mm for E. coli. The co-loading of Ripa and dfCur into a thermoresponsive chitosan hydrogel produced a synergistic platform with enhanced biocompatibility, potent antibacterial effects, and controlled drug release. This multifunctional dressing shows promise for advanced DFU management and warrants further in vivo evaluation.