title: A tale of two polymorphic pharmaceuticals: pyrithyldione and propyphenazone and their 1937 co-crystal patent.
abstract: 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 I-III of PYR and forms I and II of PROP.
authors.affiliation: Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, Johannesburg, 2050, South Africa. andreas.lemmerer@wits.ac.za
authors.forename: Andreas
authors.initials: A
authors.lastname: Lemmerer
authors.forename: Joel
authors.initials: J
authors.lastname: Bernstein
authors.forename: Ulrich J
authors.initials: UJ
authors.lastname: Griesser
authors.forename: Volker
authors.initials: V
authors.lastname: Kahlenberg
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Többens
authors.forename: Saul H
authors.initials: SH
authors.lastname: Lapidus
authors.forename: Peter W
authors.initials: PW
authors.lastname: Stephens
authors.forename: Catharine
authors.initials: C
authors.lastname: Esterhuysen
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000494:pharmacology*; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000737:chemistry; D003460:Crystallization; D011728:Pyridones / Q000737:chemistry*; D013696:Temperature; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011728:Pyridones; C005589:pyrithyldione; C009077:propyphenazone; D000983:Antipyrine