Using static method to measure tolmetin solubility at different pressures and temperatures in supercritical carbon dioxide.

Tolmetin is a non-steroidal anti-inflammatory drug being used to decrease the level of hormones which are the reasons for pain, swelling, tiredness, and stiffness for osteoarthritis and rheumatoid arthritis cases. We evaluated its solubility in supercritical carbon dioxide (SC-CO) with the aim of drug nanonization, considering temperature and pressure variations between 120 and 400 bar and 308-338 K, in the experiments. In this way, a PVT solubility cell based on static solubility approach coupled with a simple gravimetric procedure was utilized to evaluate the solubility of tolmetin. The solubility values between 5.00 × 10 and 2.59 × 10 mol fraction were obtained for tolmetin depending on the pressure and temperature of the cell. The measured data demonstrated a direct correlation between pressure and solubility of tolmetin, while the effect of temperature was a dual effect depending on the crossover pressure (160 bar). The calculated solubility data were modeled using several semi-empirical correlations, and the fitting parameters were calculated using the experimental data via appropriate optimization method. The correlated solubility data revealed that the KJ model was the most accurate one with an average absolute relative deviation percent (AARD%) of 6.9. Moreover, the carried out self-consistency analysis utilizing these correlations illustrated great potential of these models to extrapolate the solubility of tolmetin beyond the measured conditions.