Ibandronate polymorph

Abstract

The present invention relates to a new crystalline polymorph of 3-(N-methyl-N-pentyl)amino-1-hydroxypropane-1,1-diphosphonic acid monosodium salt monohydrate (Ibandronate) with the following formula

1 . A crystalline polymorph of 3-(N-methyl-N-pentyl)amino-1-hydroxypropane-1,1-diphosphonic acid monosodium salt monohydrate (Ibandronate) having an X-ray powder diffraction pattern having characteristic peaks expressed in angle 2-theta at approximately 
     
       
         
               
             
                   
               
                 Angle 2-theta 
               
                   
               
                   
               
               
             
                 9.7° 
               
                 12.2° 
               
                 14.4° 
               
                 16.8° 
               
                 25.8° 
               
                   
               
           
              
              
              
             
             
              
             
          
           
              
              
              
              
              
              
             
          
         
       
     
   
   
       2 . The crystalline polymorph of  claim 1 , having the x-ray powder diffraction pattern shown in  FIG. 1 . 
   
   
       3 . A crystalline Ibandronate polymorph having an IR absorption spectrum having characteristic peaks expressed in cm −1  at approximately 3679 cm −1 , 3164 cm −1 , 2955 cm −1 ; 2854 cm −1 , 1377 cm −1 , 1290 cm −1 , 1157 cm −1 , 1093 cm −1 , 1068 cm −1 , 1035 cm −1 , 965 cm −1 , 951 cm −1 , 933 cm −1  and 905 cm −1 , 761 cm −1  and 723 cm −1 . 
   
   
       4 . The crystalline polymorph of  claim 3 , having the IR absorption spectrum shown in  FIG. 2 . 
   
   
       5 . A crystalline Ibandronate polymorph having a characteristic peak expressed in cm −1  at approximately 2968 cm −1  in a vibrational Raman spectrum. 
   
   
       6 . The crystalline polymorph of  claim 5  having characteristic peaks expressed in cm −1  at approximately 2968 cm −1 , 2951 cm −1 , 2928 cm −1 , 2887 cm −1 , 2849 cm −1 , 1441 cm −1 , 1308 cm −1 , 1136 cm −1 , 1056 cm −1 , 1023 cm −1 , 954 cm −1 , 907 cm −1 , 839 cm −1 , 762 cm −1  and 678 cm −1  in vibrational Raman spectrum. 
   
   
       7 . The crystalline polymorph of  claim 5 , having the vibrational Raman spectrum shown in  FIG. 3 . 
   
   
       8 . Ibandronate containing at least 80% of a crystalline polymorph according to  claim 1 . 
   
   
       9 . A process for the preparation of a crystalline Ibandronate polymorph according to  claim 1  comprising crystallizing 3-(N-methyl-N-pentyl)amino-1-hydroxypropane-1,1-diphosphonic acid monosodium salt, a monohydrate, a polymorph or a mixture of polymorphs thereof at a temperature of 10° C. to 45° C. in a polar solvent and adding a polar aprotic solvent to initialize the crystallization. 
   
   
       10 . The process according to  claim 9 , wherein the polar solvent is water and the polar aprotic solvent is a member selected from the group consisting of an aliphatic ketone and a cyclic ether. 
   
   
       11 . The process according to  claim 10 , wherein the polar aprotic solvent is tetrahydrofuran. 
   
   
       12 . A pharmaceutical composition comprising a crystalline polymorph according to  claim 1  and a pharmaceutically acceptable carrier and/or adjuvant.