Antisolvent addition at extreme conditions

This article describes the use of antisolvent addition at high-pressure to aid precipitation and recovery of high-pressure phases to ambient pressure. Paracetamol (PCM) was used as a model system to demonstrate the principle due to the extensive literature of paracetamol at high-pressure and ambient pressure. We have observed that we are able to recover the orthorhombic form of paracetamol to ambient pressure using this technique, although solvent-mediated transformations are a hurdle. During this investigation we observed a new methanol solvate of paracetamol that is similar in structure to the known form. The methanol solvate is stable to 0.2 GPa before transformation to the orthorhombic form that is known to be the stable form at high pressure. Antisolvent addition at high pressure (0.8 GPa) allows crystallization and recovery to ambient pressures of metastable form II paracetamol.