Les Laboratoires Servier

Roger Fassler

Vit Lellek

Christoph Strassler

Disclosed are two new crystalline forms, &#x3b4; and &#x3b5;, 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 &#x3b5; crystalline form is obtained in the crystallization of perindopril erbumine at from 30 to 45&#xb0; C., preferably from 34 to 45&#xb0; 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&#xb0; C., and stirring is then continued for at least 15 h at from 30 to 45&#xb0; C., preferably from 35 to 37&#xb0; C., the &#x3b5; crystalline form is converted to the &#x3b4; crystalline form. The &#x3b4; crystalline form can also be obtained by stirring the &#x3b1; or &#x3b2; crystalline form at from 33 to 38&#xb0; C. in tert.-butyl methyl ether containing from 0.9 to 1.4% (v/v) water with seeding with the &#x3b4; crystalline form. The &#x3b5; crystalline form can also be obtained by stirring the &#x3b1; or &#x3b2; crystalline form at from 28 to 35&#xb0; C. in tert.-butyl methyl ether containing from 0.9 to 1.4% (v/v) water with seeding with the &#x3b5; crystalline form; or by stirring the &#x3b1; or &#x3b2; crystalline form at from 35 to 38&#xb0; C. in tert.-butyl methyl ether containing from 1.5 to 2.0% (v/v) water.

Crystalline forms of perindopril erbumine

Disclosed are two new crystalline forms, &#x3b4; and &#x3b5;, 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 &#x3b5; crystalline form is obtained in the crystallization of perindopril erbumine at from 30 to 45&#xb0; C., preferably from 34 to 45&#xb0; 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&#xb0; C., and stirring is then continued for at least 15 h at from 30 to 45&#xb0; C., preferably from 35 to 37&#xb0; C., the &#x3b5; crystalline form is converted to the &#x3b4; crystalline form. The &#x3b4; crystalline form can also be obtained by stirring the &#x3b1; or &#x3b2; crystalline form at from 33 to 38&#xb0; C. in tert.-butyl methyl ether containing from 0.9 to 1.4% (v/v) water with seeding with the &#x3b4; crystalline form. The &#x3b5; crystalline form can also be obtained by stirring the &#x3b1; or &#x3b2; crystalline form at from 28 to 35&#xb0; C. in tert.-butyl methyl ether containing from 0.9 to 1.4% (v/v) water with seeding with the &#x3b5; crystalline form; or by stirring the &#x3b1; or &#x3b2; crystalline form at from 35 to 38&#xb0; C. in tert.-butyl methyl ether containing from 1.5 to 2.0% (v/v) water.

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Langwiesen, Switzerland

Roger Fassler