Ramipril formulation

• US 20070259941A1
• Filed: 11/15/2005
• Published: 11/08/2007
• 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:
  US11/273,575
• Publication Number:
  US 20070259941A1
• Time in Patent Office: Days
• US Class Current: 514/412
• 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: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• 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 Ramipril formulation which is basic.

2. The formulation of claim 1 including a stabiliser selected from the group consisting of carbonate salts, amino acids with basic side chains, and amines.

3. The formulation of claim 1 wherein the stabliser is selected from the group consisting of arginine, ethanolamine, sodium lauryl sulphate, talc, magnesium staerate, sodium carbonate, sodium bicarbonate, calcium carbonate and citrate salts.

4. The formulation of claim 1 wherein the pH of the formulation is greater than 7.5.

5. The formulation of claim 4 wherein the pH of the formulation is greater than 8.

6. The formulation of claim 1 wherein degradation to ramipril diketopiperazine during storage at 25°

C. and 60% RH for 3 months is less than 1%.

7. The formulation of claim 1 wherein degradation to ramipril diketopiperazine during storage at 25°

C. and 60% RH for 3 months is less than 0.5%.

8. The formulation of claim 1 wherein degradation to ramipril diketopiperazine during storage at 40°

C. and 75% RH for 3 months is less than 4%.

9. The formulation of claim 1 wherein degradation to ramipril diketopiperazine during storage at 40°

C. and 75% RH for 3 months is less than 2%.

10. A Ramipril formulations that displays a major degradation pathway to the active metabolite ramiprilat, rather that the inactive diketopiperazine.

11. The formulation of claim 10 wherein the major degradation pathway is obtained by the inclusion of stabilisers in the formulation that makes it basic.

12. The formulation of claim 11 including a stabiliser selected from the group consisting of carbonate salts, amino acids with basic side chains, and amines.

13. The formulation of claim 11 wherein the stabliser is selected from the group consisting of arginine, ethanolamine, sodium lauryl sulphate, talc, magnesium staerate, sodium carbonate, sodium bicarbonate, calcium carbonate and citrate salts.

14. The formulation of claim 10 wherein the formulation is in a liquid form and includes ethanolamine as a stabiliser.

15. The ramipril formulation of claim 10 wherein the formulation additionally comprises a diuretic.

16. The formulation of claim 10 wherein the pH of the formulation is greater than 7.5.

17. The formulation of claim 10 wherein the pH of the formulation is greater than 8.

18. A ramipril formulation that demonstrates substantially no degradation to ramipril diketopiperazine during storage.

19. The formulation of claim 18 wherein degradation to ramipril diketopiperazine during storage at 25°

C. and 60% RH for 3 months is less than 1%.

20. The formulation of claim 18 wherein degradation to ramipril diketopiperazine during storage at 25°

C. and 60% RH for 3 months is less than 0.5%.

21. The formulation of claim 18 wherein degradation to ramipril diketopiperazine during storage at 40°

C. and 75% RH for 3 months is less than 4%.

22. The formulation of claim 18 wherein degradation to ramipril diketopiperazine during storage at 40°

C. and 75% RH for 3 months is less than 2%.

23. A method for treating or preventing a disease in a mammal selected from the group consisting of hypertension, heart failure, stroke, myocardial infarction, diabetes and cardiovascular disease or for reducing the risk of further strokes, heart attacks and cognitive impairment among stroke patients comprising administering to a mammal in need of such treatment the formulation of 19.

24. A therapeutic package suitable for commercial sale, comprising a container, a basic Ramipril formulation, and, associated with said container, notice advising of extended shelf life.

25. A method for the manufacture of a ramipril formulation including the step of adding at least one basic compound.

26. The method of claim 25 wherein the basic compound is a citrate salt, L-arginine, or a carbonate salt.

27. The method of claim 26 wherein the basic compound is a citrate salt.

28. The method of claim 25 wherein the method additionally includes the step of wet granulation, dry granulation or direct compression.

29. The method of claim 25 wherein the method includes the step of wet granulation.