Abstract
Tolfenamic acid (TFA) has been used until recently in prevention and treatment of diseases with the pain and inflammation symptoms. It also showed an inhibitory activity to the growth of cancer cells in pancreas. However, use of TFA was ceased due to a number of side effects, and today it is not used in clinical practice. Conformational polymorphism of TFA makes it unique regarding possible modifications of its polymorphic forms, and till now new forms can be revealed. One of the methods of accessing different polymorphic modifications is applying supercritical fluidic techniques using the scCO2 medium. The present paper reports the analysis of the spatial structure and conformational preferences of TFA in DMSO‑d6 (at 25 °C and 0.1 MPa) and in a mixed solvent scCO2 + DMSO (45 °C and 9 MPa) based on nuclear Overhauser effect spectroscopy. The results demonstrate changes in the conformer fractions depending on the medium used and thermodynamic parameters of state, which provides important control means for obtaining new polymorphic modifications.
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