Novel Crystalline Form of Atorvastatin Hemi-calcium Salt, Hydrate Thereof, And Method of Producing The Same

Abstract

The present invention provides a novel crystalline form of [R-(R*,R*)]-2-(4-fluorophenyl)-β,δ-dihydroxy-5-(1-mthylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-heptanoic acid hemi-calcium salt (atorvastatin hemi-calcium salt) of the following formula 1, which is known to be useful as a drug, a hydrate thereof and a preparation method thereof:

1 - 9 . (canceled) 
     
     
         10 . A crystalline Form α atorvastatin hemi-calcium salt characterized by having peaks having a relative intensity greater than 10% at 2θ values of 8.8, 9.6, 11.9, 16.9, 19.6, 21.7, 23.5, and 29.7±0.5° in an X-ray powder diffraction measured using CuKα radiation. 
     
     
         11 . The crystalline Form α atorvastatin hemi-calcium salt of  claim 10 , characterized by having peaks having a relative intensity greater than 10% at 2θ values of 8.8, 9.6, 11.9, 16.9, 19.6, 21.7, 23.5 and 29.7±0.5° in the X-ray powder diffraction. 
     
     
         12 . The crystalline Form α atorvastatin hemi-calcium salt of  claim 10 , characterized by having broad peaks at 2θ values of 8.8, 9.6, 16.9, 21.7 and 23.5±0.5° in the X-ray powder diffraction. 
     
     
         13 . The crystalline Form α atorvastatin hemi-calcium salt of  claim 10 , characterized by showing the X-ray powder diffraction spectrum as shown in  FIG. 2 . 
     
     
         14 . The crystalline Form α atorvastatin hemi-calcium salt of  claim 10 , characterized by showing the solid-state  13 C NMR spectrum as shown in  FIG. 3 . 
     
     
         15 . The hydrate form of the crystalline form α atorvastatin hemi-calcium salt, as according to  claim 10 . 
     
     
         16 . The hydrate form of the crystalline form α atorvastatin hemi-calcium salt, as according to  claim 11 . 
     
     
         17 . The hydrate form of the crystalline form α atorvastatin hemi-calcium salt, as according to  claim 12 . 
     
     
         18 . The hydrate form of the crystalline form α atorvastatin hemi-calcium salt, as according to  claim 13 . 
     
     
         19 . The hydrate form of the crystalline form α atorvastatin hemi-calcium salt, as according to  claim 14 . 
     
     
         20 . A method for preparing a crystalline Form α atorvastatin hemi-calcium salt or a hydrate thereof, comprising the steps of: suspending a crude atorvastatin hemi-calcium salt in a mixed solvent of methanol and water; and stirring the suspension at a reaction temperature of 5˜25° C. for 1-10 hours. 
     
     
         21 . The method of  claim 20 , wherein the volume ratio of methanol: water in the mixed solvent is 1:10(v/v)˜1:15(v/v), and the ratio of volume of the mixed solvent:weight of the crude atorvastatin hemi-calcium salt is 1:60˜65(v/wt). 
     
     
         22 . The method of  claim 20 , wherein the reaction temperature is 10˜20° C. 
     
     
         23 . The method of  claim 20 , wherein the stirring is carried out for 1-5 hours.