Solubility of fluorinated pharmaceuticals in dense carbon dioxide

The solubilities of benzoic acid and fluorinated benzoic acid derivatives i n dense carbon dioxide mere measured at 35 and 55 degrees C to find out how much fluorination increases the solubility of organic pharmaceuticals in d ense carbon dioxide. The solubilities of two higher molecular weight pharma ceuticals, triflupromazine and flufenamic acid, in dense carbon dioxide wer e also measured. The solubility of benzoic acid is approximately 0.2 wt % a t 35 degrees C and 100 bar. Attaching one fluorine atom increased the solub ility 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 degrees C and 103 bar. Introduction of a trifluoromethyl group increased the solubility significantly, and the solubility of 3-(trifluoro methyl)benzoic acid in dense carbon dioxide at 35 degrees 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 w as relatively high, i.e., 4.4 wt % at 43 degrees C and 145 bar. Flufenamic acid was very sparingly soluble at ambient temperatures (<50 degrees C), an d 70-80 degrees C was necessary to reach 1-3 wt % solubility. These experim ents show that dense carbon dioxide is a feasible solvent for fluorinated p harmaceuticals and that the fluorine content of a compound can be used as a clue to find carbon dioxide soluble molecules.