Oxygen-impervious packaging with optional oxygen scavenger, stabilized thyroid hormone compositions and methods for storing thyroid hormone pharmaceutical compositions

• US 20060183804A1
• Filed: 12/22/2005
• Published: 08/17/2006
• Est. Priority Date: 12/27/2004
• Status: Abandoned Application

• Current Assignee: King Pharmaceuticals Research And Development Incorporated (Pfizer Inc.)
• Original Assignee: King Pharmaceuticals Research And Development Incorporated (Pfizer Inc.)
• Inventors: Rutledge, Dan, Brinkman, Kyle R., Bayman, Joseph R.
• Application Number:
  US11/317,063
• Publication Number:
  US 20060183804A1
• Time in Patent Office: Days
• US Class Current: 514/567
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4

Abstract

Novel packaging, methods of packaging and methods for storing thyroid hormone pharmaceutical compositions, such as levothyroxine (T₄) sodium and liothyronine (T₃) sodium, in reduced oxygen conditions for maintaining the stability and potency of the thyroid hormones during extended shelf life are provided.

Claims

1. A thyroid hormone pharmaceutical composition in solid unit oral dosage form comprising an effective amount of levothyroxine for treating a human in need of levothyroxine treatment and a pharmaceutical excipient, wherein said thyroid hormone pharmaceutical composition, when stored in a sealed oxygen impermeable container after about 90 days of storage at accelerated aging conditions, has a thyroid hormone potency which is at least about 3.5% greater than when said thyroid hormone pharmaceutical composition is stored in a sealed oxygen permeable container under similar accelerated aging conditions.

2. The composition of claim 1, wherein said effective amount of thyroid hormone is selected from the group consisting of 25 μ

g, 50 μ

g, 75 μ

g, 88 μ

g, 100 μ

g, 112 μ

g, 125 μ

g, 137 μ

g, 150 μ

g, 175 μ

g, 200 μ

g, and 300 μ

g.

3. The composition of claim 1, wherein the oxygen impermeable container comprises polyethylene teraphthalate (PET).

4. A thyroid hormone pharmaceutical composition comprising an effective amount of thyroid hormone for treating a human in need of thyroid hormone treatment and a pharmaceutical excipient, wherein said thyroid hormone pharmaceutical composition, when stored in a sealed oxygen impermeable container after about 18 months of storage at customary storage conditions, has a thyroid hormone potency which is at least about 3.5% greater than when said thyroid hormone pharmaceutical composition is stored in a sealed oxygen permeable container under similar customary storage conditions.

5. The composition of claim 4, wherein said effective amount of thyroid hormone is selected from the group consisting of 25 μ

g, 50 μ

g, 75 μ

g, 88 μ

g, 100 μ

g, 112 μ

g, 125 μ

g, 137 μ

g, 150 μ

g, 175 μ

g, 200 μ

g, and 300 μ

g.

6. The composition of claim 4, wherein the oxygen impermeable container comprises polyethylene teraphthalate (PET).

7. A pharmaceutical package containing a thyroid hormone pharmaceutical composition comprising a sealable oxygen impermeable container having reduced oxygen content.

8. A pharmaceutical package of claim 7, wherein said reduced oxygen content is at most about 2%.

9. A pharmaceutical package of claim 7, wherein the sealed oxygen impermeable container comprises a body having a hollow interior and an opening, and the body comprises an oxygen impermeable material.

10. A pharmaceutical package of claim 7, wherein the oxygen impermeable container comprises polyethylene teraphthalate (PET).

11. A pharmaceutical package of claim 10, wherein the container has reduced or minimal head-space.

12. A pharmaceutical package containing a thyroid hormone pharmaceutical in solid unit oral dosage form comprising:

a sealed oxygen impermeable container having reduced oxygen content, wherein said thyroid hormone pharmaceutical composition has a thyroid hormone potency which is at least about 3.5% greater after about 18 months of storage in said sealed oxygen impermeable container at customary storage conditions, than when said thyroid hormone pharmaceutical composition is stored in a sealed oxygen permeable container under customary storage conditions.

13. A pharmaceutical package of claim 12, wherein the sealed oxygen impermeable container comprises a body having a hollow interior and an opening, and the body comprises an oxygen impermeable material.

14. A pharmaceutical package of claim 12, wherein the oxygen impermeable container comprises polyethylene teraphthalate (PET).

15. A pharmaceutical package of claim 14, wherein the container has reduced or minimal head-space.

16. A method of packaging a thyroid hormone pharmaceutical composition in solid unit oral dosage form, said method comprising:

(1) depositing said thyroid hormone pharmaceutical composition in an oxygen impermeable container under reduced oxygen conditions; and

(2) sealing the container.

17. A thyroid hormone pharmaceutical composition in solid unit oral dosage form comprising an effective amount of thyroid hormone for treating a human in need of thyroid hormone treatment and a pharmaceutical excipient, wherein said thyroid hormone pharmaceutical composition is stored in a sealed oxygen impermeable container, wherein said container is purged with nitrogen to remove oxygen before being sealed.

18. A pharmaceutical package containing a thyroid hormone pharmaceutical composition in solid unit oral dosage form comprising a sealed oxygen impermeable container purged with nitrogen to remove oxygen before being sealed, wherein said thyroid hormone pharmaceutical composition has a thyroid hormone potency which is at least about 21.6% greater after about 28 days of storage at accelerated aging conditions in said sealed oxygen impermeable container, than when said thyroid hormone pharmaceutical composition is stored under accelerated aging conditions for the same period of time in a sealed oxygen permeable container which is not purged with inert gas to remove oxygen before being sealed.

19. A method of packaging a thyroid hormone pharmaceutical composition in solid unit oral dosage form comprising:

(1) depositing said thyroid hormone pharmaceutical composition within a container;

(2) purging the container with inert gas to remove oxygen; and

(3) sealing the container.

20. A thyroid hormone pharmaceutical composition in solid unit oral dosage form comprising an effective amount of thyroid hormone for treating a human in need of thyroid hormone treatment and a pharmaceutical excipient, wherein said thyroid hormone pharmaceutical composition, when stored in a sealed container comprising an oxygen scavenger after about 90 days of storage at accelerated aging conditions, has a thyroid hormone potency which is at least about 8.3% greater than when said thyroid hormone pharmaceutical composition is stored in a sealed container which does not comprise an oxygen scavenger under similar accelerated aging conditions.

21. A pharmaceutical package containing a thyroid hormone pharmaceutical composition comprising a sealed container having reduced oxygen content, further comprising an oxygen scavenger, wherein said thyroid hormone pharmaceutical composition has a thyroid hormone potency which is at least about 8.3% greater after about 90 days of storage in said container at accelerated aging conditions, than when said thyroid hormone pharmaceutical composition is stored in a sealed container which does not comprise an oxygen scavenger under similar accelerated aging conditions.

22. A method of packaging a thyroid hormone pharmaceutical composition in solid unit oral dosage form to provide increased thyroid hormone potency after about 90 days of storage at accelerated aging conditions, comprising:

(1) depositing said thyroid hormone pharmaceutical composition in a container with an oxygen scavenger under reduced oxygen conditions; and

(2) sealing the container;

to provide a thyroid hormone pharmaceutical composition having a thyroid hormone potency which is at least about 8.3% greater after about 90 days of storage in said sealed container at accelerated aging conditions, than when said thyroid hormone pharmaceutical composition is stored in a sealed container which does not comprise an oxygen scavenger for about 90 days under accelerated aging conditions.