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A Tale of Two Polymorphic Pharmaceuticals: Pyrithyldione and Propyphenazone and their 1937 Co‐crystal Patent
Author(s) -
Lemmerer Andreas,
Bernstein Joel,
Griesser Ulrich J.,
Kahlenberg Volker,
Többens Daniel M.,
Lapidus Saul H.,
Stephens Peter W.,
Esterhuysen Catharine
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201100667
Subject(s) - active ingredient , crystal (programming language) , crystal structure , chemistry , polymorphism (computer science) , stereochemistry , crystallography , bioinformatics , biology , biochemistry , computer science , genotype , gene , programming language
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(1 H ,3 H )‐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‐3 H ‐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.