Manipulating the size, the morphology and the polymorphism of acetaminophen using supercritical antisolvent (SAS) precipitation

The supercritical antisolvent technology is used to crystallize paracetamol particles. Supercritical carbon dioxide (scCO2) is used as antisolvent. Ethanol, acetone and mixtures of ethanol and acetone are used as solvents. The initial concentration of paracetamol in the solution was varied between 1 and 5 wt%, the composition of the ethanol/acetone solvent mixture between 50 and 90 wt% of ethanol and the operation pressure between 10 and 16 MPa at a temperature of 313 K. The most important finding is that the polymorph of paracetamol crystals can be adjusted between monoclinic and orthorhombic by varying the content of ethanol in the solution. The second important finding is that the occurrence of primary and secondary crystal structures can be explained solely by the overall supersaturation during the crystallization process. While X-ray diffraction was used to analyze the polymorph of the particles, their morphology was analyzed using scanning electron microscopy.