Pharmaceutical formulae for thyroid hormones and procedures for obtaining them

• US 7,691,411 B2
• Filed: 12/23/2003
• Issued: 04/06/2010
• Est. Priority Date: 12/27/2002
• Status: Active Grant

• Current Assignee: Altergon SA
• Original Assignee: Altergon SA
• Inventors: Di Martino, Alessandro, Mateo, Angel, Marchiorri, Maurizio, Garavani, Alberto
• Primary Examiner(s): Sheikh; Humera N
• Application Number:
  US10/746,386
• Publication Number:
  US 20040219218A1
• Time in Patent Office: 2,296 Days
• Field of Search: 424/400, 424/451, 424/464, 424/484, 424/488
• US Class Current: 424/488
• CPC Class Codes: A61K 9/2063 Proteins, e.g. gelatin
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4

Abstract

The present invention provides pharmaceutical formulation for thyroid hormones which allow safe and stable administration by mouth within the ambit of the narrow therapeutic index prescribed in the case of thyroid dysfunctions, as well as procedures for obtaining them.

Claims

1. A pharmaceutical composition in the form of a single phase uniform matrix of soft-gel for oral administration comprising thyroid hormones as active principle selected from the group consisting of T3, T4, their sodium salts and mixtures thereof in a concentration of 0.001 to 1% by weight, the single phase uniform matrix of soft-gel comprising in the dried state 30%-68% by weight of gelatine of bovine, pig or fish origin, 31-60% by weight of glycerol and 1-10% by weight of water.

2. Pharmaceutical composition according to claim 1, characterised in that it comprises, in the dried state, 32-55% by weight of glycerol and 1-10% by weight of water.

3. Pharmaceutical composition according to claim 2, characterised in that it comprises, in the dried state, 32.5-50% by weight of glycerol and 1-10% by weight of water.

4. Pharmaceutical composition according to claim 1, wherein the gelatine has a pH between 3 and 10.

5. Pharmaceutical composition according to claim 2, wherein the gelatine has a pH between 3 and 10.

6. Pharmaceutical composition according to claim 3, wherein the gelatine has a pH between 3 and 10.

7. Pharmaceutical composition according to claim 1, characterised in that it comprises 0.5-5% by weight of ethanol.

8. Pharmaceutical composition according to claim 1, characterised in that it comprises, in the dried state, 3-10% by weight of polyhydroxy or polyether alcohols, selected from the group consisting of sorbitol/sorbitans, 1,2-propyleneglycol, polyethyleneglycols, mannitol, and mixtures thereof.

9. Pharmaceutical composition according to claim 2, characterised in that it comprises, in the dried state, 3-10% by weight of polyhydroxy or polyether alcohols, selected from the group consisting of sorbitans, 1,2-propyleneglycol, polyethyleneglycols, mannitol, and mixtures thereof.

10. Pharmaceutical composition according to claim 3, characterised in that it comprises, in the dried state, 3-10% by weight of polyhydroxy or polyether alcohols, selected from the group consisting of sorbitol/sorbitans, 1,2-propyleneglycol, polyethyleneglycols, mannitol, and mixtures thereof.

11. Pharmaceutical composition according to claim 5, characterised in that it comprises, in the dried state, 3-10% by weight of polyhydroxy or polyether alcohols, selected from the group consisting of sorbitol/sorbitans, 1,2-propyleneglycol, polyethyleneglycols, mannitol, and mixtures thereof.

12. Pharmaceutical composition according to claim 1, further comprising one or more members selected from the group consisting of excipients, solid additives that modify the characteristics of the release of thyroid hormones from the uniform matrix of soft-gel, preservatives and colouring agents.

13. Pharmaceutical composition according to claim 2, further comprising one or more members selected from the group consisting of excipients, solid additives that modify the characteristics of the release of thyroid hormones from the uniform matrix of soft-gel, preservatives and colouring agents.

14. Pharmaceutical composition according to claim 3, further comprising one or more members selected from the group consisting of excipients, solid additives that modify the characteristics of the release of thyroid hormones from the uniform matrix of soft-gel, preservatives and colouring agents.

15. Pharmaceutical composition according to claim 5, further comprising one or more members selected from the group consisting of solid additives that modify the characteristics of the release of thyroid hormones from the uniform matrix of soft-gel, preservatives and colouring agents.

16. A pharmaceutical composition in the form of a single phase uniform matrix of a soft-gel for oral administration comprising a thyroid hormone, selected from the group consisting of T3, T4, their sodium salts, and mixtures thereof, as active principle in a concentration of 0.001-1% by weight, the single phase uniform matrix of soft-gel comprising, in the dried state, 30%-70% by weight of gelatine of bovine, pig or fish origin, 20-60% by weight of sorbitol/sorbitans, and 1-10% by weight of water.

17. Pharmaceutical composition according to claim 16, characterised in that it comprises, in the dried state, 25-55% by weight of sorbitol/sorbitans and 1-10% by weight of water.

18. Pharmaceutical composition according to claim 17, characterised in that it comprises, in the dried state, 25%-50% by weight of sorbitol/sorbitans and 1-10% by weight of water.

19. Pharmaceutical composition according to claim 16, wherein the gelatine has a pH between 3 and 10.

20. Pharmaceutical composition according to claim 17, wherein the gelatine has a pH between 3 and 10.

21. Pharmaceutical composition according to claim 18, wherein the gelatine has a pH between 3 and 10.

22. Pharmaceutical composition according to claim 16, characterised in that it comprises 0.5-5% in weight of ethanol.

23. Pharmaceutical composition according to claim 17, characterised in that it comprises 0.5-5% in weight of ethanol.

24. Pharmaceutical composition according to claim 18, characterised in that it comprises 0.5-5% in weight of ethanol.

25. Pharmaceutical composition according to claim 16, characterised in that it comprises, in the dried state, 1-10% by weight of polyhydroxy or polyether alcohols, selected from the group consisting of glycerol, 1,2-propyleneglycol, polyethyleneglycols, mannitol, and mixtures thereof.

26. Pharmaceutical composition according to claim 17, characterised in that it comprises, in the dried state, 1-10% by weight of polyhydroxy or polyether alcohols, selected from the group consisting of glycerol, 1,2-propyleneglycol, polyethyleneglycols, mannitol, and mixtures thereof.

27. Pharmaceutical composition according to claim 18, characterised in that it comprises, in the dried state, 1-10% by weight of polyhydroxy or polyether alcohols, selected from the group consisting of glycerol, 1,2-propyleneglycol, polyethyleneglycols, mannitol, and mixtures thereof.

28. Pharmaceutical composition according to claim 22, characterised in that it comprises, in the dried state, 1-10% by weight of polyhydroxy or polyether alcohols, selected from the group consisting of glycerol, 1,2-propyleneglycol, polyethyleneglycols, mannitol, and or mixtures thereof

29. Pharmaceutical composition according to claim 16, further comprising one or more members selected from the group consisting of solid additives that modify the characteristics of the release of thyroid hormones from the uniform matrix of soft-gel, preservatives and colouring agents.

30. Pharmaceutical composition according to claim 17, further comprising one or more members selected from the group consisting of solid additives that modify the characteristics of the release of thyroid hormones from the uniform matrix of soft-gel, preservatives and colouring agents.

31. Pharmaceutical composition according to claim 18, further comprising one or more members selected from the group consisting of solid additives that modify the characteristics of the release of thyroid hormones from the uniform matrix of soft-gel, preservatives and colouring agents.

32. Pharmaceutical composition according to claim 22, further comprising one or more members selected from the group consisting of solid additives that modify the characteristics of the release of thyroid hormones from the uniform matrix of soft-gel, preservatives and colouring agents.