Solubility and solubilization properties of non-steroidal anti-inflammatory drugs

Ten non-steroidal anti-inflammatory drugs (NSAID) of the acetic and propionic classes were analyzed in the form of salts to disclose the solubilization property of their aqueous solutions toward a lipid probe (the azo-dye Orange OT). This property is related to the self-aggregation of the anions above a concentration value that differs for each drug: indomethacin and fenclofenac showed solubilization ability in the form of sodium salts in pure water (starting from 30 and 40 mM, respectively); these values decreased with increasing ionic strength. In the case of diclofenac it was necessary to use a salt prepared with an organic base, that displayed a solubility higher than that of the sodium salt, required to overcome the critical value (35 mM). Naproxen, sulindac, ketoprofen, indoprofen were used at high concentrations of their sodium salts (100-160 mM) and solubilize the dye in the presence of a high total ionic strength. Alclofenac did not display solubilization ability; fenbufen and ibuprofen were tested as salts of an organic base: results were not conclusive because the presence of the organic base in the salt form and in the solution, as added electrolyte for the ionic strength, affected the results of the solubilization tests. The results are briefly discussed in terms of hydrophilic/hydrophobic balance present on the anion of the NSAID examined, as evaluated by the fragment constant approach.