Process for the Preparation of Gadobenate Dimeglumine Complex in a Solid Form

Abstract

The present invention discloses a process for the preparation of gadobenate dimeglumine complex in a solid form. In particular, said solid form is conveniently obtained by spray-drying a corresponding liquid suspension at a given temperature and concentration. The present invention is particularly advantageous for the industrial scale as the solid form may be obtained by employing water as a solvent, which is a non-toxic solvent, easy to handle and basically not requiring troublesome health or safety precautions.

1 . A process for the preparation of a solid form of gadobenate dimeglumine compound of formula (I): 
       
         
           
           
               
               
           
         
         comprising spray-drying a liquid composition of said compound. 
       
     
     
         2 . The process according to  claim 1 , wherein said liquid composition has a concentration of at least 0.2 M gadobenate dimeglumine. 
     
     
         3 . The process according to  claim 2 , wherein said concentration is comprised from 0.45 M to 0.55 M. 
     
     
         4 . The process according to  claim 1 , wherein the liquid composition is an aqueous solution. 
     
     
         5 . The process according to  claim 4 , wherein said aqueous solution is a purified water solution. 
     
     
         6 . The process according to  claim 1 , wherein the inlet temperature (T-inlet) of the spray-drier is comprised from 140° C. to 280° C., and the outlet temperature (T-outlet) is comprised from 70° C. to 120° C. 
     
     
         7 . The process according to any one of  claims 1 ,  4 ,  5  and  16 , comprising an atomization of the liquid composition by using a pressure or a two-fluid nozzle. 
     
     
         8 . A solid powdery form of gadobenate dimeglumine prepared by the process according to any one of claims 1, 4, 5 and 16. 
     
     
         9 . The solid form of gadobenate dimeglumine according to  claim 8 , characterised in that it is a water soluble powder comprising gadobenate dimeglumine having a particle size from 1 μm to 200 μm. 
     
     
         10 . The solid form gadobenate dimeglumine according to  claim 8 , characterised in that the particle size is from 20 μm to 70 μm. 
     
     
         11 . A pharmaceutical kit comprising a first container containing the spray-dried gadobenate dimeglumine according to  claim 8 , and a second container containing a physiologically acceptable aqueous carrier. 
     
     
         12 . The pharmaceutical kit according to  claim 11 , wherein said physiologically acceptable aqueous carrier is water for injection. 
     
     
         13 . A process for the preparation of a solid form of 4-carboxy-5,8,11-tris(carboxymethyl1)-1-phenyl-2-oxa-5,8,11-triazatridecan-13-oic acid, comprising spray-drying a liquid composition of said compound. 
     
     
         14 . The process according to  claim 13 , wherein said liquid composition is an aqueous solution. 
     
     
         15 . The process according to any one of  claims 13 - 14 , wherein the concentration of said solution is from 7% w/w to 14% w/w. 
     
     
         16 . The process according to  claim 2 , wherein the liquid composition is an aqueous solution. 
     
     
         17 . A pharmaceutical kit comprising a first container containing the spray-dried gadobenate dimeglumine according to  claim 10 , and a second container containing a physiologically acceptable aqueous carrier.