NOVEL CRYSTALLINE FORMS OF PERINDOPRIL ERBUMINE

Disclosed are two novel crystalline forms d and e of perindopril erbumine, which are suitable as therapeutic substances in medicaments used for treating cardiovascular diseases, especially high blood pressure and cardiac insufficiency. Crystalline form e is obtained by crystallizing perindopril erbumine from MTBE containing 1.5 to 2.5 percent (v/v) of water at 30 to 45 degree C, preferably 34 to 45 degree C, crystallization expediently taking place by stirring. Crystalline form e changes into crystalline form d if the water is removed, practically by azeotropic distillation, preferably at 35 to 37 degree C, and stirring continues for at least 15 h at 30 to 45 degree C, preferably 35 to 37 degree C. Crystalline form d can also be obtained by stirring crystalline form a or ß in tert-butyl methyl ether containing 0.9 to 1.4 percent (v/v) of water at 33 to 38 degree C while inoculating the same with crystalline form d. Crystalline form e can further be obtained by stirring crystalline form a or ß in tert-butyl methyl ether containing 0.9 to 1.4 percent (v/v) of water at 28 to 35 degree C while inoculating the same with crystalline form e, or by stirring crystalline form a or ß in tert-butyl methyl ether containing 1.5 to 2.0 percent (v/v) of water at 35 to 38 degree C. Se describen dos novedosas formas cristalinas ( y ( de perindopril erbumina, las cuales son apropiadas como sustancias terapeuticas en medicamentos usados para tratar enfermedades cardiovasculares, especialmente alta presion sanguinea e insuficiencia cardiaca. La forma cristalina ( se obtiene cristalizando perindopril erbumina a partir de MTBE que contiene de 1.5 a 2.5 % (v/v) de agua a entre 30 y 45 degree C, preferiblemente desde 34 hasta 45 degree C, la cristalizacion tiene lugar oportunamente por agitacion. La forma ( cristalina cambia a forma ( cristalina si se elimina el agua, practicamente mediante destilacion azeotropica, preferiblemente desde 35 hasta 37 degree C, y la agitacion continua durante al menos 15 horas de 30 a 45 degree C, preferiblemente de 35 a 37 degree C. La forma ( cristalina tambien puede obtenerse agitando la forma ( o ( cristalina en eter metilico de tert-butilo que contenga de 0.9 a 1.4 % (v/v) de agua, desde 33 hasta 38 degree C, mientras se inocula la misma con la forma ( cristalina. La forma ( cristalina puede obtenerse ademas agitando la forma ( o ( cristalina en eter metilico de tert-butilo con contenido de 0.9 a 1.4 % (v/v) de agua, desde 28 hasta 35 degree C,