Solubility of Tolbutamide and Chlorpropamide in Supercritical Carbon Dioxide

Tolbutamide and chlorpropamide are oral hypoglycemic drugs that are used to treat diabetic patients. In the context of employing these drugs in green pharmaceutical applications that make use of supercritical fluids, the solubility of tolbutamide and chlorpropamide in supercritical CO₂ has been measured at 313.15, 333.15, and 353.15 K and in the pressure range of 10–30 MPa. A semiflow apparatus equipped with a continuous solvent-dilution device of the depressurization line, which avoids the solubility data to be underestimated, was employed. The solubility of tolbutamide is in the range of 1.66 × 10^–5 to 40.5 × 10^–5 mole fraction while that of chlorpropamide is in the range of 2.29 × 10^–6 to 72.2 × 10^–6 mole fraction, which indicates that the first drug has higher solubility in the supercritical fluid than the latter, probably due to its higher hydrophobicity. The results were successfully correlated with the most popular empirical and semiempirical models reported in the literature. The Sparks model provided the best correlation for chlorpropamide with an adjusted absolute average percent deviation (AARD%) of 3.5%, while the Keshmiri model provided the best correlation for tolbutamide, with an AARD% of 4.8%. The self-consistency of the experimental data was checked through the Méndez-Santiago and Teja model.