(352f) Measurement and Correlation of Solubility of Methylsalicylic Acid Isomers in Supercritical Carbon Dioxide

Salicylic acid and its derivatives, such as methylsalicylic acid, are well-known active pharmaceutical ingredients for different medical treatments and model compounds for investigation of the thermodynamic behavior of dissolution and crystallization. For example, 4-methylsalicylic acid can inhibit tyrosinase activity and thus is beneficial to slow the formation of melanin in food; the effect of 5-methylsalicylic acid on the agglomeration behavior of surface-active ionic liquid. The solubility of these compounds in supercritical carbon dioxide is important for the design of relevant processes and validation of predictive thermodynamic models. In this study, a semi-flow type of high-pressure apparatus was constructed to measure the solubility of isomers of methylsalicylic acid in supercritical carbon dioxide. The solubility of salicylic acid in supercritical carbon dioxide was measured to validate the reliability of the apparatus and experimental procedure. The results of salicylic acid show a well satisfactory agreement with experimental data reported in literature. Using the same experimental apparatus and procedure, the solubility of three methylsalicylic acid isomers, 3-methylsalicylic acid, 4-methylsalicylic acid, and 5-methylsalicylic acid, were measured at 308.15, 318.15 and 328.15 K over a pressure range of 85 - 185 bar. The results show that the solubility of methylsalicylic acid isomers is between 10^-6 and 10^-4. These newly measured solubility data of were correlated by semi-empirical models, such as Chrastil model and MST (Mendez Santiago and Teja) model, and cubic equations of state, such as Peng-Robinson equation of state. The consistency of solubility data was confirmed by the good correlation results obtained with the Chrastil model and MST model.