Polymorphism of tedisamil dihydrochloride.
The results of studies on tedisamil dihydrochloride in the solid state demonstrate that the compound occurs in three polymorphic forms. The three modifications have been characterized by thermomicroscopy, differential scanning calorimetry (DSC), vibrational spectroscopy, solid-state nuclear magnetic resonance (NMR), and X-ray powder diffractometry (XRPD). The thermodynamic relationships are illustrated in a semischematic energy/temperature diagram that gives information about the relative stability and physical properties of the three modifications between 0 K and the melting temperatures. The three modifications are enantiotropically related. Modification II, the material obtained during manufacturing, is the thermodynamically stable crystal form at 20 degrees C. The thermodynamic transition point of mod II with I (instant melting point: 248-250 degrees C) is between 100 and approximately 140 degrees C (DeltaH(t,II/I) = 4.4+/-0.8 kJ/mol (95% CI)). A phase transition of mod II (probably into mod III) was detected thermomicroscopically at about -180 degrees C. The thermodynamic transition point of mod III with I was determined to be at -9 to -6 degrees C. Because mods I and III are thermodynamically and kinetically unstable at ambient conditions, these crystal forms are of analytical interest.
Henck
J O
JO
Institut für Pharmakognosie der Universität Innsbruck, Josef-Moeller-Haus, Innrain 52, A-6020 Innsbruck, Austria. Jan-Olav.Henck.JH@bayer-ag.de
Finner
E
E
Burger
A
A
D000889:Anti-Arrhythmia Agents / Q000737:chemistry*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D018360:Crystallography, X-Ray; D003521:Cyclopropanes / Q000737:chemistry*; D005583:Fourier Analysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008853:Microscopy / Q000379:methods; D008968:Molecular Conformation; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman / Q000379:methods; D013237:Stereoisomerism; D013696:Temperature; D013816:Thermodynamics
D000889:Anti-Arrhythmia Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003521:Cyclopropanes; C059921:tedisamil