Ramipril Formulation

• US 20070098782A1
• Filed: 08/24/2006
• Published: 05/03/2007
• Est. Priority Date: 10/28/2005
• Status: Abandoned Application

• Current Assignee: Selamine Limited (Abbvie Incorporated)
• Original Assignee: Selamine Limited (Abbvie Incorporated)
• Inventors: Harrison, Paul, Power, Anna
• Application Number:
  US11/508,916
• Publication Number:
  US 20070098782A1
• Time in Patent Office: Days
• US Class Current: 424/451
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/403 condensed with carbocyclic rings, e.g. carbazole
• CPC Class Codes: A61K 31/405 Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

A Ramipril formulation which is suitably stabilised to control the degradation to the active metabolite ramiprilat.

Claims

1. A solid dosage form comprising ramipril and a pharmaceutically acceptable carrier, wherein at least 50% of the ramipril is in the form of a sodium or potassium ramipril salt and the pharmaceutical carrier is selected from the group consisting of calcium sulphate, calcium carbonate and a mixture thereof.

2. The solid dosage form of claim 1, wherein at least 70% of the ramipril is in the form of a ramipril salt.

3. The solid dosage form of claim 1, wherein at least 80% of the ramipril is in the form of a ramipril salt.

4. The solid dosage form of claim 1, wherein at least 90% of the ramipril is in the form of a ramipril salt.

5. The solid dosage form of claim 1, wherein at least 95% of the ramipril is in the form of a ramipril salt.

6. The solid dosage form of claim 1, wherein at least 98% of the ramipril is in the form of a ramipril salt.

7. The solid dosage form of claim 1, wherein the salt is the sodium salt.

8. The solid dosage form of claim 1 in the form of a tablet.

9. The solid dosage form of claim 1 in the form of a capsule.

10. A method of making a ramipril formulation, comprising obtaining a ramipril salt and incorporating the ramipril salt into the formulation, wherein at least 50% by weight of the ramipril is in the form of a sodium or potassium ramipril salt and wherein the formulation comprises a pharmaceutical carrier selected from the group consisting of calcium sulphate, calcium carbonate and a mixture thereof.

11. The method of claim 10, wherein the formulation is in solid dosage form.

12. The method of claim 11, wherein the solid dosage form is a tablet.

13. The method of claim 11, wherein the solid dosage form is a capsule.

14. The method of claim 10, wherein at least 70% by weight of the ramipril is in the form of a ramipril salt.

15. The method of claim 10, wherein at least 80% by weight of the ramipril is in the form of a ramipril salt.

16. The method of claim 10, wherein at least 90% by weight of the ramipril is in the form of a ramipril salt.

17. The method of claim 10, wherein at least 95% by weight of the ramipril is in the form of a ramipril salt.

18. The method of claim 10, wherein at least 98% by weight of the ramipril is in the form of a ramipril salt.

19. The method of claim 10, comprising:

adding ramipril to an aqueous solvent;

converting the ramipril into a salt of ramipril;

dissolving the salt of ramipril in the aqueous solvent; and

removing the solvent, to yield dried ramipril salt.

20. The method of claim 19, wherein the aqueous solvent consists essentially of water.

21. The method of claim 20, wherein the solvent comprises a mixture of water and alcohol.

22. The method of claim 20 wherein the solvent comprises a mixture of water and ethanol.

23. The method of claim 19, wherein the method comprises dispersing ramipril particles in the aqueous solvent.

24. The method of claim 19, wherein the method comprises adding an alkali to the solvent to convert the ramipril into the ramipril salt.

25. The method of claim 19, wherein the method comprises adding sodium hydrogen carbonate to the solvent to convert the ramipril into the ramipril salt.

26. The method of claim 19, wherein the method comprises converting at least 50% of the ramipril into the ramipril salt.

27. The method of claim 19, wherein the method comprises converting at least 70% of the ramipril into the ramipril salt.

28. The method of claim 19, wherein the method comprises converting at least 80% of the ramipril into the ramipril salt.

29. The method of claim 19, wherein the method comprises converting at least 90% of the ramipril into the ramipril salt.

30. The method of claim 19, wherein the method comprises converting at least 95% of the ramipril into the ramipril salt.

31. The method of claim 19, wherein the method comprises converting at least 98% of the ramipril into the ramipril salt.

32. The method of claim 19, wherein the converting comprises maintaining the ramipril in the aqueous solvent in the presence of a metal compound for sufficient time that substantially all the ramipril is converted into ramipril salt.

34. A solid dosage form comprising a sodium or potassium ramipril salt and a pharmaceutical carrier selected from the group consisting of calcium sulphate, calcium carbonate and a mixture thereof, obtained by the method of claim 10.

33. A solid dosage formulation comprising ramipril and a pharmaceutically acceptable carrier, obtained by making the formulation out of a ramipril preparation, wherein at least 50% of the ramipril in the ramipril preparation is in the form of a sodium or potassium ramipril salt and the pharmaceutical carrier is selected from the group consisting of calcium sulphate, calcium carbonate and a mixture thereof.