Crystalline forms of zofenopril calcium

1. Zofenopril calcium form F characterised by

an XRPD spectrum comprising at least six of the following 2θ peaks: 4.6, 6.0, 8.3, 10.2, 14.5, 16.5, 17.1, 18.2, 19.9, 21.4 and 23.5±0.2 degrees 2θ.

2. Zofenopril calcium form F according to claim 1 , characterised by:

(i) an XRPD spectrum substantially as shown in FIG. 4 ; and/or

(ii) a DSC trace substantially as shown in FIG. 5 .

3. Zofenopril calcium form F according to claim 1 , comprising less than 10% of zofenopril calcium in other polymorphic or amorphous forms.

4. Zofenopril calcium form F according to claim 1 , having a differential scanning calorimetry (DSC) with an endothermic peak at about 200° C.

5. Zofenopril calcium form F according to claim 1 , having a thermo-gravimetric analysis (TGA) trace substantially as shown in FIG. 6 .

6. Zofenopril calcium form F according to claim 1 , comprising less than 1% of zofenopril calcium in other polymorphic or amorphous forms.

7. A pharmaceutical composition comprising zofenopril calcium according to claim 1 and a pharmaceutically acceptable excipient.

8. A process for preparing zofenopril calcium form F according to claim 1 , comprising the steps of:

(a) dissolving an amine salt of zofenopril in a water miscible organic solvent;

(b) mixing the solution obtained in step (a) with an aqueous solution of a calcium salt; and

(c) isolating the zofenopril calcium form F.

9. The process according to claim 8 , wherein the amine salt of zofenopril is

selected from the group consisting of dicyclohexylamine, cyclohexylamine, benzylamine, N-methylbenzylamine and α-methylbenzylamine salts.

10. The process according to claim 8 , wherein the water miscible organic solvent is an alcohol, an ether, a cyclic ether, a ketone or an amide.

11. The process according to claim 10 , wherein the water miscible organic solvent is

a straight-chain, branched or cyclic C1 to C6 alcohol.

12. The process according to claim 10 , wherein the water miscible organic solvent is

a cyclic ether.

13. The process according to claim 10 , wherein the water miscible organic solvent is

an amide.

14. The process according to claim 8 , wherein the calcium salt in step (b) is

selected from the group consisting of fluoride, chloride, bromide, iodide, oxide, hydroxide, carbonate, nitrate, sulfate, and acetate salts.

15. The process according to claim 8 , wherein steps (a) and (b) are carried out at a temperature of up to 60° C.

16. A method of treating or preventing a disorder wherein inhibiting an angiotensin converting enzyme (ACE) is beneficial, the method comprising administering to a patient in need thereof a therapeutically or prophylactically effective amount of zofenopril calcium according to claim 1 , wherein the disorder is selected from hypertension, cardiac decompensation, myocardial infarction, acute myocardial infarction, heart failure or chronic heart failure.

17. A method of treating or preventing a disorder wherein inhibiting an angiotensin converting enzyme (ACE) is beneficial, the method comprising administering to a patient in need thereof a therapeutically or prophylactically effective amount of a pharmaceutical composition according to claim 7 , wherein the disorder is selected from hypertension, cardiac decompensation, myocardial infarction, acute myocardial infarction, heart failure or chronic heart failure.