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

We report on the crystallization of acetaminophen using the supercritical antisolvent process. For systems forming crystalline structures, the mechanisms governing crystallization in the SAS process are yet not fully understood. The aim of this study is to further investigate into the crystallization by the SAS process. Considering the non-ideal SAS solute paracetamol (acetaminophen, PCM), the influence of classical SAS parameters like initial solute concentration and pressure on the supersaturation and therefore the characteristics of the generated PCM crystals are analyzed. The most important finding is that the polymorph of paracetamol crystals can be adjusted between monoclinic and orthorhombic by varying the solvent composition of 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.