Reassessment of paracetamol orthorhombic Form III and determination of a novel low‐temperature monoclinic Form III‐m from powder diffraction data

摘要

Paracetamol [ N ‐(4‐hydroxyphenyl)acetamide, C 8 H 9 NO 2 ] has several polymorphs, just like many other drugs. The most stable polymorphs, denoted Forms I and II, can be obtained easily and their crystal structures are known. Crystals of the orthorhombic, less stable, room‐temperature Form III are difficult to grow; they need a special recipe to crystallize and suffer from severe preferred orientation. A crystal structure model of Form III has been proposed and solved from a combination of structure prediction and powder X‐ray diffraction (PXRD) [Perrin et al. (2009). Chem. Commun. 22 , 3181–3183]. The final R wp value of 0.138 and the corresponding considerable residual trace were reasons to check its validity. A new structure determination of Form III using new high‐resolution PXRD data led to a final R wp value of 0.042 and an improvement of the earlier proposed model. In addition, a reversible phase transition was found at 170–220?K between the orthorhombic Form III and a novel monoclinic Form III‐m. The crystal structure of Form III‐m has been determined and refined from PXRD data to a final R wp value of 0.059.