Screening of conformational polymorphism of ibuprofen in supercritical CO2

The populations of conformers of ibuprofen in supercritical CO2 have been calculated for two isochors in the temperature range of 35–90°C, using the combination of data of IR spectroscopy, quantum chemical calculations and molecular dynamics simulation (metadynamics approach). The results of 2D cross-correlation analysis of IR spectra confirm the presence of two spectral contributions associated with two conformers. The population of the first conformer (Conf. I) is found to be dominating within the investigated temperature range. Moreover, at the temperature of 60°C, for both studied isochors, the population of the first conformer reaches the maximum. The assumption about the correlation between the populations of conformers in supercritical media and population of polymorphs, which form during crystallization from certain initial state parameters, has been formulated and checked using analysis of micronized ibuprofen powder obtained by the method of rapid expansion of supercritical solution (RESS). The analysis of the microcrystalline ibuprofen, obtained by RESS, was performed by Differential Scanning Calorimetry (DSC) and X-Ray Powder Diffraction (XRPD). Both methods lead to estimation of the polymorphs populations in accordance with the conformer populations at corresponding state parameters. [Display omitted] •Population of ibuprofen conformers in scCO2 under isochoric heating was calculated.•Ibuprofen conformers were studied by quantum-chemical calculations and MD simulation.•XRPD and DSC were used to analyze the microcrystalline ibuprofen obtained upon RESS.•Correlation between conformational manifold and polymorphism of ibuprofen was found.