Development of a novel intramuscular liposomal injection for advanced meloxicam delivery: Preparation, characterization, in vivo pharmacokinetics, pharmacodynamics, and pain assessment in an orthopedic pain model

Abstract

Pain produces several physiological, and degenerative complications. This study aimed to formulate meloxicam (MLX) in liposomes to increase solubility and deliver MLX in a controlled manner to overcome its poor aqueous solubility and relatively short t_1/2 problems. Liposomes were prepared by thin film hydration followed by ultrasonication. Tests for characterizing formulations included particle size, span, entrapment efficiency, drug loading, stability, differential scanning calorimetry (DSC), Fourier transformation infrared (FT-IR) spectroscopy, morphology, <i>in vitro</i> release, release kinetics mathematical modeling, and an <i>in vivo</i> pain model in dogs undergoing orthopedic surgeries, followed by <i>in vivo</i> pharmacokinetics, pharmacodynamics, and pain assessment studies in comparison to the reference standard, Mobitil®. Liposomal MLX had a particle size of around 100 nm, 82 % entrapment efficiency, and 4.62 % drug loading. Stability studies, DSC, and FT-IR spectroscopy indicated that liposomes were highly stable. The formulation showed an improved <i>in vitro</i> controlled release pattern and an enhanced <i>in vivo</i> pharmacokinetic behavior as manifested by higher t_1/2 and AUC₀ _- ₂₄ and lower Cl/F in comparison to Mobitil®. The pharmacodynamics study and pain scales demonstrated liposomal MLX managed postoperative pain better than Mobitil®. In conclusion, the incorporation of MLX in liposomes increased its solubility and stability, as well as its pain management properties.