Characterization of polymorphs and solvates of 3-amino-1-(m-trifluoromethylphenyl)-6-methyl-1H-pyridazin-4-one.
The characterization of two polymorphs of the title compound (F2692; 1) by differential scanning calorimetry (DSC), microanalysis, proton nuclear magnetic resonance spectroscopy, thermogravimetry, thermomicroscopy, infrared spectroscopy, and X-ray diffractometry is described. Both polymorphs are crystalline, with form II being more stable at temperatures less than 160 degrees C. The thermal behavior was studied at different rates of heating, and the enthalpies of transition were calculated from DSC data. The transformation of aqueous suspensions of form I to the water-stable form II is described, and the heats of solution and intrinsic aqueous dissolution rates of both polymorphs were determined. 1 also formed solvates with dimethyl sulfoxide and 1-methyl-2-pyrrolidinone. The solvates were studied by thermogravimetry, DSC, and infrared spectroscopy.
Laboratoire de Chimie Générale et Minérale, Faculté de Pharmacie, Montpellier, France.
A
A
Chauvet
J
J
Masse
J P
JP
Ribet
D
D
Bigg
J M
JM
Autin
J L
JL
Maurel
J F
JF
Patoiseau
J
J
Jaud
D014151:Anti-Anxiety Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004355:Drug Stability; D006358:Hot Temperature; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D011110:Polymorphism, Genetic; D011522:Protons; D011724:Pyridazines / Q000737:chemistry*; D011760:Pyrrolidinones / Q000737:chemistry; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013818:Thermogravimetry; D014961:X-Ray Diffraction
D014151:Anti-Anxiety Agents; D011522:Protons; D011724:Pyridazines; D011760:Pyrrolidinones; C077138:F 2692; C038678:N-methylpyrrolidone; D004121:Dimethyl Sulfoxide