Crystalline and amorphous form of a triazolo(4,5-d)pyrimidine compound

Abstract

The invention provides new forms of a chemical compound of formula (I). The invention relates to forms fo a chemical compound (I), in particular to crystalline and amorphous forms, more particularly four crystalline forms and an amorphous form. The invention further relates to processes for the preparation of such forms, to pharmaceutical compositions comprising the compound in crystalline and/or amorphous form and to therapeutic use of such forms.

1 . A compound of formula (I):  
       
         
           
           
               
               
           
         
       
       in a substantially crystalline form.  
     
     
         2 . A compound of formula (I) as claimed in  claim 1  that exists in a substantially anhydrous form.  
     
     
         3 . A compound of formula (I) as claimed in  claim 1 , characterised by an X-ray powder diffraction pattern containing specific peaks of high intensity at 5.3° (±0.1°), 20.1° (±0.1°), 20.7° (±0.1°), 21.0° (±0.1°) and 21.3° (±0.1°) 2θ.  
     
     
         4 . A compound of formula (I) as claimed in  claim 1  or  3 , characterised by an X-ray powder diffraction pattern containing specific peaks at 5.3° (±0.1°), 8.0° (±0.1°), 9.6° (±0.1°), 13.9° (±0.1°), 15.3° (±0.1°), 20.1° (±0.1), 20.7° (±0.1°), 21.0° (±0.1°), 21.3° (±0.1°), 26.2° (±0.1°) and 27.5° (±0.1°) 2θ.  
     
     
         5 . A compound of formula (I) as claimed in any one of claims  1 ,  3  or  4 , characterised by a differential scanning calorimetry curve to have an onset of melting which is in the range 146-152° C.  
     
     
         6 . A compound of formula (I) as claimed in  claim 1 , characterised by an X-ray powder diffraction pattern containing specific peaks of high intensity at 5.5° (±0.1°), 13.5° (±0.1°), 18.3° (±0.1°), 22.7° (±0.1°) and 24.3° (±0.1°) 2θ.  
     
     
         7 . A compound of formula (I) as claimed in  claim 1  or  6 , characterised by an X-ray powder diffraction pattern containing specific peaks at 5.5° (±0.1°), 6.8° (±0.1°), 10.6° (±0.1°), 13.5° (±0.1°), 14.9° (±0.1°), 18.3° (±0.1°), 19.2° (±0.1°), 22.7° (±0.1°), 24.3° (±0.1°) and 27.1° (±0.1°) 2θ.  
     
     
         8 . A compound of formula (I) as claimed in any one of  claims 1  to  6  or  7  characterised by a differential scanning calorimetry curve to have an onset of melting which is in the range 136-139° C.  
     
     
         9 . A compound of formula (I) as claimed in  claim 1 , characterised by an X-ray powder diffraction pattern containing specific peaks of high intensity at 14.0° (±0.1°), 17.4° (±0.1°), 18.4° (±0.1°), 21.4° (±0.1°) and 24.1°(±0.1°) 2θ.  
     
     
         10 . A compound of formula (I) as claimed in claims  1  or  9 , characterised by an X-ray powder diffraction pattern containing specific peaks at 5.6° (±0.1°), 12.5° (±0.1°), 14.0° (±0.1°), 17.4° (±0.1°), 18.4° (±0.1°), 21.4° (±0.1°), 22.2° (±0.1°), 22.9° (±0.1°), 24.1° (±0.1°) and 24.5° (±0.1) 2θ.  
     
     
         11 . A compound of formula (I) as claimed in any one of claims  1 ,  9  or  10  characterised by a differential scanning calorimetry curve to have an onset of melting which is in the range 127-132° C.  
     
     
         12 . A compound of formula (I) as claimed in  claim 1 , characterised by an X-ray powder diffraction pattern containing specific peaks of high intensity at 4.9° (±0.1°), 9.2° (±0.1°), 11.6° (±0.1°), 15.6° (±0.1°) and 16.4° (±0.1°) 2θ.  
     
     
         13 . A compound of formula (I) as claimed in  claim 1  or  12  characterised by an X-ray powder diffraction pattern containing specific peaks at 4.9° (±0.1°), 6.0° (±0.1°), 9.2° (±0.1°), 11.6° (±0.1°), 12.8° (±0.1°), 15.6° (±0.1°), 16.4° (±0.1°), 17.2° (±0.1°) and 18.1°  
     
     
         14 . A compound of formula (I) as claimed in any one of claims  1 ,  12  or  13  characterised by a differential scanning calorimetry curve to have an onset of melting which at approximately 139° C.  
     
     
         15 . A compound of formula (I) in a substantially amorphous form.  
     
     
         16 . A compound of formula (I) which is in the form of a hydrate.  
     
     
         17 . A mixture of a compound of formula (I) as claimed in any one of  claims 6  to  8  and a compound of formula (I) as claimed in any one of  claims 9  to  11 .  
     
     
         18 . A process for the preparation of a compound as claimed in  claim 1 , wherein the compound of formula (I) is crystallised from a solvent selected from the group: lower alkyl acetates, lower alkyl alcohols, aliphatic and aromatic hydrocarbons, dialkyl ethers, dialkyl ketones, acetonitrile, water, or a mixture thereof.  
     
     
         19 . A process as claimed in  claim 18 , wherein the solvent is selected from the group: ethanol, ethyl acetate, iso-propanol, iso-octane, acetonitrile, water, or a mixture thereof.  
     
     
         20 . A process as claimed in  claim 19 , wherein the solvent is selected from the group: a mixture of methanol and water, ethanol, ethyl acetate, a mixture of ethanol and water, a mixture of iso-propanol and water, a mixture of ethyl acetate and iso-octane, and acetonitrile.  
     
     
         21 . A process for the production of a compound as claimed in any one of  claims 3  to  5  according to any one of  claims 18  to  20  in which the solvent is a mixture of methanol and water.  
     
     
         22 . A process for the production of a compound as claimed in any one of  claims 3  to  5  using seed.  
     
     
         23 . A process according to  claim 22  in which the seed is prepared by melting a compound as claimed in any one of  claims 6  to  8 .  
     
     
         24 . A process for the production of a compound as claimed in any one of  claims 6  to  8  according to any one of  claims 18  to  20 , in which the solvent is ethyl acetate.  
     
     
         25 . A process for the production of a compound as claimed in any one of  claims 9  to  11  according to any one of  claims 18  to  20 , in which the solvent is an alcohol.  
     
     
         26 . A process for the production of a compound as claimed in any one of  claims 9  to  11  which comprises slurrying a compound of formula (I) in IPA/water solvent system at a temperature of 5 to 65° C.  
     
     
         27 . A process for the production of a compound as claimed in any one of  claims 12  to  14 , which comprises a process according to any one of  claims 18  to  20 , in which the solvent is acetonitrile.  
     
     
         28 . A compound as claimed in any one of  claims 1  to  17  for use as a medicament  
     
     
         29 . A pharmaceutical composition comprising a compound as claimed in any one of  claims 1  to  17  in admixture with a pharmaceutically acceptable adjuvant, diluent or carrier.  
     
     
         30 . A pharmaceutical composition comprising a compound as claimed in any one of  claims 1  to  17  for use in the prevention of arterial thrombotic complications in patients with coronary artery, cerebrovascular or peripheral vascular disease.  
     
     
         31 . The use of a compound as claimed in any one of  claims 1  to  17  in the manufacture of a medicament for use in the prevention of arterial thrombotic complications in patients with coronary artery, cerebrovascular or peripheral vascular disease.  
     
     
         32 . A method of treatment or prevention of arterial thrombotic complications in patients with coronary artery, cerebrovascular or peripheral vascular disease, which comprises administering to a person suffering from or susceptible to such a disorder a therapeutically effective amount of a compound as claimed in any one of  claims 1  to  17 .