A Tale of Two Polymorphic Pharmaceuticals: Pyrithyldione and Propyphenazone and their 1937 Co-crystal Patent

作者：Lemmerer Andreas^*; Bernstein Joel; Griesser Ulrich J; Kahlenberg Volker; Toebbens Daniel M; Lapidus Saul H; Stephens PeterW; Esterhuysen Catharine

来源：Chemistry - A European Journal, 2011, 17(48): 13445-13460.

DOI：10.1002/chem.201100667

• co-crystals
• hot-stage microscopy
• pharmaceuticals
• polymorphism
• X-ray diffraction

A co-crystal of two polymorphic active pharmaceutical ingredients (APIs), first reported and patented in 1937, has been prepared and thoroughly characterised, including crystal structure analysis. The existence of four crystal forms of one of the APIs, the sedative and hypnotic active pharmaceutical ingredient 3,3-diethyl-2,4(1H,3H)-pyridinedione, pyrithyldione (PYR), and of three crystal forms of the co-crystal-forming second API, the non-steroidal anti-inflammatory drug 1,2-dihydro-1,5-dimethyl-4-(1-methylethyl)-2-phenyl-3H-pyrazol-3-one, propyphenazone (PROP), has been reported previously, but they have only been partly characterised. For both compounds, none of the metastable forms exist at room temperature. DSC, hot-stage microscopy, X-ray diffraction and powder synchrotron X-ray diffraction were employed to characterise the polymorphic forms and to determine the crystal structures of forms IIII of PYR and forms I and II of PROP.

• 出版日期2011-11