Amorphous and Crystalline Forms of Losartan Potassium and Process For Their Preparation

Abstract

This invention relates to novel amorphous losartan potassium, novel losartan potassium in a crystalline form that is a hydrate, novel crystalline losartan potassium Form IV and solvates thereof, novel crystalline losartan potassium Form V and solvates thereof, to processes for their preparation, to compositions containing them and to their use in medicine. This invention further relates to a novel process for preparing crystalline losartan potassium Form I and Form II.

1 . Amorphous losartan potassium.  
     
     
         2 . The amorphous losartan potassium of  claim 1  containing less than about 10% crystalline losartan potassium.  
     
     
         3 . The amorphous losartan potassium of  claim 1  essentially free of crystalline losartan potassium.  
     
     
         4 . A pharmaceutical composition comprising the amorphous losartan potassium of  claim 1  and at least one pharmaceutically acceptable excipient.  
     
     
         5 . A pharmaceutical dosage form comprising the pharmaceutical composition of  claim 4 .  
     
     
         6 . The pharmaceutical dosage form of  claim 5  wherein the dosage form is an oral dosage form.  
     
     
         7 . The pharmaceutical dosage form of  claim 6  wherein the oral dosage form is a capsule or tablet.  
     
     
         8 - 20 . (canceled)  
     
     
         21 . Losartan potassium in a crystalline form that is a hydrate.  
     
     
         22 . A pharmaceutical composition comprising the losartan potassium in a crystalline form that is a hydrate of  claim 21  and at least one pharmaceutically acceptable excipient.  
     
     
         23 . A pharmaceutical dosage form comprising the pharmaceutical composition of  claim 22 .  
     
     
         24 . The pharmaceutical dosage form of  claim 23  wherein the dosage form is an oral dosage form.  
     
     
         25 . The pharmaceutical dosage form of  claim 24  wherein the oral dosage form is a capsule or tablet.  
     
     
         26 . (canceled)  
     
     
         27 . The losartan potassium of  claim 21  that is losartan potassium Form III.  
     
     
         28 . The losartan potassium of  claim 27  wherein the losartan potassium Form III is a tetrahydrate.  
     
     
         29 . The losartan potassium of  claim 28  characterized by a water content of from about 12 to about 16%.  
     
     
         30 . The losartan potassium of  claim 29  characterized by a water content of about 14%.  
     
     
         31 . Losartan potassium in a crystalline form characterized by a powder x-ray diffraction pattern with peaks at about 5.7, 8.9, 13.3, 17.5, 20.0, and 21.1±0.2 degrees two-theta.  
     
     
         32 . The losartan potassium of  claim 31  having a powder x-ray diffraction pattern substantially as depicted in  FIG. 4 .  
     
     
         33 - 36 . (canceled)  
     
     
         37 . Losartan potassium Form IV and solvates thereof.  
     
     
         38 . The losartan potassium of  claim 37  wherein the solvate is an ethanolate.  
     
     
         39 . A pharmaceutical composition comprising the losartan potassium Form IV and solvates thereof of  claim 37  and at least one pharmaceutically acceptable excipient.  
     
     
         40 . A pharmaceutical dosage form comprising the pharmaceutical composition of  claim 39 .  
     
     
         41 . The pharmaceutical dosage form of  claim 40  wherein the dosage form is an oral dosage form.  
     
     
         42 . The pharmaceutical dosage form of  claim 41  wherein the oral dosage form is a capsule or tablet.  
     
     
         43 . (canceled)  
     
     
         44 . Losartan potassium in a crystalline form characterized by a powder x-ray diffraction pattern with peaks at about 4.3, 15.6, and 23.4±0.2 degrees two-theta.  
     
     
         45 . The losartan potassium of  claim 44  having a powder x-ray diffraction pattern substantially as depicted in  FIG. 6 .  
     
     
         46 . Losartan potassium in a crystalline form having a differential scanning calorimetric thermogram with endothermic peaks at about 78° C., 218° C., 240° C., and 255° C.  
     
     
         47 . The losartan potassium of  claim 46  having a differential scanning calorimetric thermogram substantially as depicted in  FIG. 7 .  
     
     
         48 - 52 . (canceled)  
     
     
         53 . Losartan potassium Form V and solvates thereof.  
     
     
         54 . The losartan potassium of  claim 53  wherein the solvate is an ethanolate.  
     
     
         55 . A pharmaceutical composition comprising the losartan potassium Form V and solvates thereof of  claim 53  and at least one pharmaceutically acceptable excipient.  
     
     
         56 . A pharmaceutical dosage form comprising the pharmaceutical composition of  claim 55 .  
     
     
         57 . The pharmaceutical dosage form of  claim 56  wherein the dosage form is an oral dosage form.  
     
     
         58 . The pharmaceutical dosage form of  claim 57  wherein the oral dosage form is a capsule or tablet.  
     
     
         59 . (canceled)  
     
     
         60 . Losartan potassium in a crystalline form characterized by a powder x-ray diffraction pattern with peaks at about 6.4, 12.2, 20.7, 21.5, and 22.5±0.2 degrees two-theta.  
     
     
         61 . The losartan potassium of  claim 60  having a powder x-ray diffraction pattern substantially as depicted in  FIG. 8 .  
     
     
         62 - 81 . (canceled)