Process for the crystalization of losartan

A process for the crystallization of losartan potassium comprising the steps of:

• a) distilling an isopropanol-water mixture containing losartan potassium to about 2.4 to about 2.8% water content;
• b) cooling the mixture to between about 65.degree. and about 70.degree. C.;
• c) adding about a 0.5% by weight finely-milled losartan potassium in cyclohexane slurry at between about 60.degree. and about 65.degree. C. at a rate of about 0.3 l/min. to the vessel until the cloud point is reached at about 1.8 to about 2.3% water content;
• d) aging the mixture for about ten minutes;
• e) adding about 3 to about 10% by weight finely-milled losartan potassium to seed the mixture at a temperature range of about 60.degree. C. to about 70.degree. C.;
• f) aging the seeded mixture for about 1 to about 2 hours at a temperature range of about 60.degree. C. to reflux while stirring;
• g) adding about a 60.degree.-65.degree. C. solution of cyclohexane over about a two hour period maintaining a temperature of about 68.degree. C. for the mixture;
• h) distilling the mixture at a constant volume to a water content of about 0.5%, while maintaining the constant volume by addition of between about a 50:50 and a 80:20 volume to volume ratio of cyclohexane and isopropanol;
• i) distilling the mixture to a slurry density of about 200 g/l and a water content of about less than 0.1%, while adding cyclohexane to maintain about a volume to volume ratio of between about a 50:50 to about a 60:40 cyclohexane:
• isopropanol, if necessary;
• j) cooling the mixture to between about 20.degree. C. and about 30.degree. C.;
• k) filtering the mixture to isolate the crystalline losartan potassium;
• l) washing the crystalline material with 75:25 cyclohexane:
• isopropanol;
• m) washing the crystalline material with cyclohexane;
• and
• n) drying the crystalline losartan potassium under vacuum at a temperature of about 45.degree. to about 50.degree. C.