This work examines the combined influence of the supercritical fluid environment and state parameters (pressure and temperature) on the ratio of «closed» and «open» conformers of the anti-androgenic drug compound bicalutamide. NMR spectroscopy methods, including 1H and 1D NOESY, were used for the analysis. The results showed that in supercritical carbon dioxide at 45 °C and 9 MPa, the «closed» group of conformers predominates (80.9 %), while the share of «open» conformers is 19.1 %. At the same time, changing the state parameters to 55 °C and 12.5 MPa shifts the conformational equilibrium and increases the proportion of «open» conformers to 37.3 %. A study combining experiments and computer modelling of bicalutamide has improved our understanding of how weak non-covalent interactions help stabilize different shapes of the molecule. From a practical perspective, this study opens up new prospects for modifying existing and obtaining new solid forms of bicalutamide with improved characteristics.
