α crystalline form of the arginine salt of perindopril, a process for its preparation and pharmaceutical compositions containing it
View Patent ↗α-crystalline form of the compound of formula (I): characterized by its powder X-ray diffraction diagram. Medicinal products containing the same which are useful as inhibitors of angiotensin I converting enzyme.
1. An α-crystalline form of the L-arginine salt of perindopril of formula (I):
exhibiting essentially the following powder X-ray diffraction peaks, measured using a diffractometer with a copper anti-cathode and expressed in terms of Bragg's angle 2 theta (°): 4.5, 7.9 and 13.5.
2. The α-crystalline form of the compound of formula (I) according to claim 1 , characterised by the following powder X-ray diffraction peaks, measured using a diffractometer with a copper anti-cathode and expressed in terms of Bragg's angle 2 theta)(°): 4.5, 7.9, 13.5, 17.5 and 20.6.
3. The a-crystalline form of the compound of formula (I) of claim 1 , exhibiting essentially the following powder X-ray diffraction diagram measured using a diffractometer (copper anticathode) and expressed in terms of inter-planar distance d, Bragg's angle 2 theta, intensity and relative intensity (expressed as a percentage of the most intense line):
Inter-planar
Relative intensity
Angle 2 theta (°)
distance d (Å)
Intensity
(%)
4.52
19.53
2211
88.7
7.94
11.12
2080
83.5
12.152
7.277
682
27.4
13.480
6.563
2492
100.0
14.029
6.308
422
16.9
14.948
5.922
552
22.1
15.873
5.579
493
19.8
17.531
5.055
1600
64.2
18.787
4.719
363
14.5
19.579
4.530
1078
43.3
20.635
4.301
1794
72.0
22.616
3.928
798
32.0
23.367
3.804
473
19.0
23.807
3.735
362
14.5
24.434
3.640
409
16.4
27.148
3.282
450
18.1
28.214
3.160
417
16.7
4. A process for the preparation of the α-crystalline form of the compound of formula (I) of claims 1 , wherein perindopril is dissolved in water with L-arginine, and an apolar solvent and a polar solvent are added, wherein the apolar solvent is selected from methylcvclohexane, cyclohexane and toluene, and the polar solvent is selected from dimethyl sulphoxide, N,N-dimethylformamide, N,N-dimethylacetamide and N-methyl-2-pyrrolidinone, and the crystals obtained are filtered off, washed and dried.
5. The process of claim 4 , wherein the apolar solvent is methylcyclohexane and the polar solvent is dimethyl sulphoxide.
6. A pharmaceutical composition comprising as active ingredient the compound of claim 1 , in combination with one or more pharmaceutically acceptable, inert, non-toxic carriers.
7. The pharmaceutical composition of claim 6 , further comprising a diuretic.
8. The pharmaceutical composition of claim 7 , wherein the diuretic is indapamide.
9. A method for treating arterial hypertension and heart failure, comprising the step of administering to a living animal body, including a human, a therapeutically effective amount of the compound of claim 1 .