Solubility of Fluorinated Pharmaceuticals in Dense Carbon Dioxide

The solubilities of benzoic acid and fluorinated benzoic acid derivatives in dense carbon dioxide were measured at 35 and 55 °C to find out how much fluorination increases the solubility of organic pharmaceuticals in dense carbon dioxide. The solubilities of two higher molecular weight pharmaceuticals, triflupromazine and flufenamic acid, in dense carbon dioxide were also measured. The solubility of benzoic acid is approximately 0.2 wt % at 35 °C and 100 bar. Attaching one fluorine atom increased the solubility of benzoic acid slightly, and the solubility of 3-fluorobenzoic acid was approximately 1 wt %. The solubility of 3,4-difluorobenzoic acid was 1.3 wt % at 35 °C and 103 bar. Introduction of a trifluoromethyl group increased the solubility significantly, and the solubility of 3-(trifluoromethyl)benzoic acid in dense carbon dioxide at 35 °C and 100 bar was approximately 7 wt %, which is almost 40 times higher than the solubility of benzoic acid in the same conditions. The solubility of triflupromazine was relatively high, i.e., 4.4 wt % at 43 °C and 145 bar. Flufenamic acid was very sparingly soluble at ambient temperatures (