Polymorphism and conformations of mefenamic acid in supercritical carbon dioxide

[Display omitted] •Combination of IR and Raman spectroscopy and quantum chemical calculations.•Correlation of mefenamic acid polymorphs and conformers in supercritical solution.•Possibility monitoring the polymorphic transformation of mefenamic acid.•Monitoring of MA conformers in a supercritical fluid solution. In this paper we have studied the conformations of mefenamic acid molecules in its saturated solution in supercritical carbon dioxide being in contact with bottom phase containing different polymorphs of mefenamic acid under isochoric heating conditions in the temperature range of 80–220 °C. For this purpose, we used in situ IR and Raman spectroscopy as well as micro IR and micro Raman spectroscopy and quantum chemical calculations. We have found that there is a correlation between the polymorphic modifications of the crystalline form of mefenamic acid and its conformers in CO2 fluid phase. The results of this work have shown that it is possible to monitor the polymorphic transformation of the crystalline phase of mefenamic acid by screening its molecular conformations in a fluid solution. This finding opens up the possibilities to manage the obtaining of certain polymorph of mefenamic acid with high purity degree from its fluid solution by means of variation of thermodynamic parameters of this solution.