Structure and physicochemical properties of meloxicam, a new NSAID

The physicochemical properties of meloxicam, a new NSAID, were investigated. Dependent on pH and solvents used, X-ray crystallography showed that meloxicam crystallized in four different prototropic forms; the anion, the acidic enol, the zwitterion and the cation forms. As determined by 1H- and 13C-NMR, meloxicam in neutral or weakly basic solution exists in the anion form. An equilibrium between the enol and zwitterion forms, dependent upon solvent polarity, was indicated. Meloxicam was soluble at neutral pH but became rapidly insoluble with decreasing pH. At very low pH its solubility increased, indicating a second pKa value and the existen of a cation species. The very low solubility of meloxicam in acidic environments suggests it may cause few local gastrointestinal adverse events. The n-octanol-water partition coefficients (log P values) of meloxicam and other NSAIDs were estimated. At low pH meloxicam was more lipophilic than piroxicam or tenoxicam and similar to ketoprofen and naproxen.