Concentrated Liquid Thyroid Hormone Composition

• US 20090270507A1
• Filed: 01/05/2007
• Published: 10/29/2009
• Est. Priority Date: 01/06/2006
• Status: Active Grant

• Current Assignee: Intervet International BV (Merck & Co., Inc.)
• Original Assignee: Intervet International BV (Merck & Co., Inc.)
• Inventors: Pierres, Cecile, Gaugain-Hamidi, Atimad
• Granted Patent: US 8,318,712 B2
• 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: A61K 47/08 containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 47/40 Cyclodextrins; Derivatives thereof
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4

Abstract

This invention is directed generally to a liquid pharmaceutical composition comprising at least one thyroid hormone (particularly a composition further comprising at least one cyclodextrin compound), a process for making such a composition and a method of using such a composition to treat a condition associated with impaired thyroid hormone function.

Claims

1. A liquid pharmaceutical composition, wherein:

the composition comprises;

at least one thyroid hormone,

hydroxypropyl-β

-cyclodextrin,

at least one buffer, and

at least 5% (by weight) water; and

the pH of the composition is from about 8 to about 12.

2. The composition of claim 1, wherein the pH of the composition is from about 9 to about 10.5.

3. The composition of claim 2, wherein the pH of the composition is from about 10.1 to about 10.3.

4. The composition of claim 1, wherein the thyroid hormone comprises levothyroxine or a pharmaceutically acceptable salt thereof.

5. The composition of claim 1, wherein the hydroxypropyl-β

-cyclodextrin concentration is from about 10% to about 50% (by weight).

6. The composition of claim 1, wherein the composition further comprises NaOH.

7. The composition of claim 1, wherein the buffer has a pKa of at least about 9.5.

8. The composition of claim 1, wherein the buffer provides pH stability at a pH of from about 10.0 to about 10.5.

9. The composition of claim 1, wherein the buffer comprises sodium bicarbonate.

10. The composition of claim 1, wherein the composition further comprises a preservative at a concentration of no greater than about 30% (by weight).

11. The composition claim 1, wherein the composition further comprises from about 5% to about 30% (by weight) ethanol.

12. The composition of claim 1, wherein the composition further comprises from about 5% to about 20% (by weight) ethanol.

13. The composition of claim 1, wherein the composition further comprises a pharmaceutically acceptable antioxidant at a concentration of no greater than about 5% (by weight).

16. A method of treating a disorder associated with impaired thyroid hormone function in an animal, wherein the method comprises administering a therapeutically effective amount of a composition of claim 1 to the animal.

17. The method of claim 16, wherein the animal is a dog.

18. The method of claim 16, wherein the condition comprises hypothyroidism.

14. A liquid pharmaceutical composition, wherein the composition comprises:

at least one thyroid hormone,

greater than 1% (by weight) hydroxypropyl-α

-cyclodextrin,

at least one buffer, and

at least 5% (by weight) water.

15. The composition of claim 14, wherein the hydroxypropyl-β

-cyclodextrin concentration is from about 10% to about 50% (by weight).

20. A method of treating a disorder associated with impaired thyroid hormone function in an animal, wherein the method comprises administering a therapeutically effective amount of a composition of claim 14 to the animal.

21. The method of claim 20, wherein the animal is a dog.

19. (canceled)