NOVEL CRYSTALLINE FORMS OF PERINDOPRIL ERBUMINE

• Main Authors: VIT LELLEK, ROGER FAESSLER, CHRISTOPH STRAESSLER
• Format: Patent
• Language: English; Portuguese
• Published: 16.04.2012
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

Disclosed are two new crystalline forms, δ and , of perindopril erbumine. Those forms are suitable as therapeutic active substances for medicaments for the treatment of cardiovascular diseases, especially high blood pressure and heart failure. The crystalline form is obtained in the crystallization of perindopril erbumine at from 30 to 45° C., preferably from 34 to 45° C., from MTBE containing from 1.5 to 2.5% (v/v) water; the crystallization is advantageously carried out with stirring. If the water is then removed, advantageously by azeotropic distillation, preferably at from 35 to 37° C., and stirring is then continued for at least 15 h at from 30 to 45° C., preferably from 35 to 37° C., the crystalline form is converted to the δ crystalline form. The δ crystalline form can also be obtained by stirring the α or crystalline form at from 33 to 38° C. in tert.-butyl methyl ether containing from 0.9 to 1.4% (v/v) water with seeding with the δ crystalline form. The crystalline form can also be obtained by stirring the α or crystalline form at from 28 to 35° C. in tert.-butyl methyl ether containing from 0.9 to 1.4% (v/v) water with seeding with the crystalline form; or by stirring the α or crystalline form at from 35 to 38° C. in tert.-butyl methyl ether containing from 1.5 to 2.0% (v/v) water.