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Abstract

This study investigates the use of the solvent evaporation technique for developing co-crystals of Lornoxicam with Trimesic Acid (TA) to improve solubility, flowability, and drug release characteristics. Among the methods explored, solvent evaporation proved to be the most effective for producing co-crystals with enhanced physicochemical properties. Saturation solubility studies showed that while pure Lornoxicam had a solubility of 5.98 mg/mL, the co-crystal formulation LXM-TA CFIII achieved a 13.52-fold increase, indicating significant improvement. Crystals obtained through the solvent drop method demonstrated superior flow properties compared to those prepared via co-grinding or solvent evaporation. In vitro drug release studies revealed that pure Lornoxicam released 86.3% of its content within 360 minutes, whereas LXM-TA CFIII released up to 98.2%. This formulation followed a non-Fickian release mechanism, confirmed by a high regression value (R² = 0.999) and a release exponent (n = 0.793), indicating both diffusion and erosion-based release. In vivo testing on male albino mice showed that LXM-TA CFIII, administered at doses of 10, 20, and 30 mg/kg, led to dose-dependent improvements in protection and faster recovery times, with the 10 mg/kg dose offering the highest protective efficacy. Additionally, the role of electrolytes in matrix tablet formulation was evaluated. Sodium carbonate was identified as the most effective retardant for drug release. Formulation F14, containing an optimal level of sodium carbonate, demonstrated sustained drug release over 12 hours, supporting its use in twice-daily dosing. Overall, this research confirms the potential of cocrystallization and matrix modification techniques to enhance the bioavailability and therapeutic performance of poorly soluble drugs like Lornoxicam.