Accessing mefenamic acid form II through high-pressure recrystallization

High-pressure crystallisation has been successfully used as an alternative technique to prepare Form II of a non-steroidal anti-inflammatory drug, Mefenamic acid (MA). A single crystal of Form II, denoted as high-pressure Form II, was grown at 0.3 GPa from an ethanolic solution by using Diamond Anvil Cell. Comparison of the crystal structures shows that the efficient packing of molecules in Form II has been enabled by the structural flexibility of MA molecules. Compression studies performed on a single crystal of Form I resulted in 14 % decrease of unit cell volume up to 2.5 GPa. No phase transition was observed up to this pressure. A reconstructive phase transition is required to induce conformational changes in the structure, which is confirmed by crystallisation at high pressure results.