| 摘要 |
Disclosed are two new crystalline forms, delta and epsilon, of perindopril erbumine. Those forms are suitable as therapeutic active substances for medicaments for the treatment of cardio-vascular diseases, especially high blood pressure and heart failure. The epsilon crystalline form is obtained in the crystallisation 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 crystallisation 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 epsilon crystalline form is converted to the delta crystalline form. The delta crystalline form can also be obtained by stirring the alpha or beta 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 delta crystalline form. The epsilon crystalline form can also be obtained by stirring the alpha or beta 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 epsilon crystalline form; or by stirring the alpha or beta crystalline form at from 35 to 38° C. in tert.-butyl methyl ether containing from 1.5 to 2.0% (v/v) water.
|
