Pharmaceutical compositions comprising 1-isopropyl-3-[ (4-M-toluidino-3-pyridyl) sulphonyl] -urea as active ingredient

Abstract

The present invention concerns the use of 1-isopropyl-3-[(4-m-toluidino-3-pyridyl)sulphonyl]-urea in the pharmaceutical field. In particular, it proposes the use of a pure and stable polymorphic form of 1-isopropyl-3-[(4-m-toluidino-3-pyridyl)sulphonyl]-urea for the preparation of solid pharmaceutical forms, and likewise a method of synthesis to obtain such a pure and stable polymorphic form of 1-isopropyl-3-[(4-m-toluidino-3-pyridiyl)sulphonyl]-urea.

1 . A solid pharmaceutical formulation comprising pure and stable form II of torsemide.  
   
   
       2 . The pharmaceutical formulation according to  claim 1  in which pure and stable form II of torsemide is characterised by the fact of containing less than 1% (by weight) of contamination with form I of torsemide and by the fact of not showing detectable polymorphic transformations in the FT-IR spectrum registered in KBr after 6 months of accelerated stability testing according to ICH (at 40°±2° C./75±5% of relative humidity).  
   
   
       3 . The pharmaceutical formulation according to  claim 2  in which pure and stable form II of torsemide is characterised through the following signals in the X-ray diffractogram of the powders expressed in degrees two theta: 9.0±0.1; 9.2±0.1; 10.7±0.1; 15.9±0.1; 18.2±0.1; 18.5±0.1; 18.8±0.1; 20.4±0.1; 22.6±0.1; 23.1±0.1; 23.5±0.1.  
   
   
       4 . The pharmaceutical formulation according to  claim 3  in which the pure and stable form II of torsemide is characterised through the signals in the X-ray diffractogram of the powders expressed in degrees two theta as in table 2.  
   
   
       5 . The pharmaceutical formulation according to  claim 4  in which the pure and stable form II of torsemide is characterised through the diffractogram of the powders as in  FIG. 3 .  
   
   
       6 . The pharmaceutical formulation according to  claim 2  in which the pure and stable form II of torsemide is characterised through the following peaks in the FT-IR spectrum registered in KBr: 3354±2 cm −1 ; 3326±2 cm −1 ; 3085±2 cm −1 ; 2964±2 cm −1 ; 1617±2 cm −1 ; 1555±2 cm −1 ; 1510±2 cm −1 ; 1357±2 cm −1 ; 1326±2 cm −1 ; 1277±2 cm −1 ; 1234±2 cm −1 ; 1151±2 cm −1 ; 900±2 cm −1 ; 837±2 cm −1 .  
   
   
       7 . The pharmaceutical formulation according to  claim 6  in which the pure and stable form II of torsemide is characterised through the peaks in the FT-IR spectrum as in table 4.  
   
   
       8 . The pharmaceutical formulation according to  claim 7  in which the pure and stable form II of torsemide is characterised through the FT-IR spectrum as in  FIG. 4  or  FIG. 5 .  
   
   
       9 . The pharmaceutical formulation according to  claim 3  in which the pure and stable form II of torsemide is characterised by a melting point in the interval between 159.9° C. and 160.2° C.  
   
   
       10 . The pharmaceutical formulation according to  claim 6  in which the pure and stable form II of torsemide is characterised by a melting point in the interval between 159.9° C. and 160.2° C.  
   
   
       11 . The pharmaceutical formulation according to  claim 2  in which the pure and stable form II of torsemide is obtainable through a procedure comprising the following steps: 
 suspension of crude dried torsemide in 10 parts of deionised water;    the addition of 48% potassium hydrate solution, slowly with stirring maintaining the temperature at 20-25° C., until obtaining complete solution and without exceeding pH 12.5;    filtration of the solution thus obtained through 40 micron paper;    gradual acidification of the filtrate thus obtained by stirring with 80% acetic acid preferably until reaching a pH of 5.3-5.7 maintaining the temperature at 20-25° C. during the addition, obtaining a suspension;    stirring of the suspension for 30 minutes at a temperature of 20-25° C., suction filtration of the solid obtained and washing with water; and    drying of the solid in a dryer under vacuum at a temperature of 50° C.    
   
   
       12 - 16 . (canceled)