Liquid levothyroxine formulations

• US 9,345,772 B1
• Filed: 02/27/2015
• Issued: 05/24/2016
• Est. Priority Date: 02/27/2015
• Status: Active Grant

• Current Assignee: TAP Pharmaceuticals, AG
• Original Assignee: Nilesh Parikh, William Hite
• Inventors: Parikh, Nilesh, Hite, William
• Primary Examiner(s): Thomas, Timothy
• Application Number:
  US14/634,452
• Time in Patent Office: 452 Days
• US Class Current: 1/1
• 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 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• 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: A61K 9/08 Solutions composition of solutions A61K47/00

Abstract

Embodiments of the present invention provide levothyroxine solutions that consist of from about 0.001% w/v to about 0.01% w/v of a levothyroxine; at least 70% w/w of a glycerol; less than 30% w/w of a water; and from about 0.01% w/w to about 1.5% w/w of an ethylenediaminetetraacetic acid (EDTA). Such levothyroxine solutions are characterized by exhibiting levothyroxine storage stability.

Claims

1. A pharmaceutical solution comprising:

from 0.001% w/v to 0.01% w/v of a levothyroxine;

from 75% w/w to 95% of glycerol;

from 0.01% w/w to 1.5% w/w of an ethylenediaminetetraacetic acid (EDTA); and

an amount of water sufficient to adjust the pharmaceutical solution to 100% w/w, and

wherein the solution is storage stable.

2. The pharmaceutical solution of claim 1, wherein the levothyroxine is levothyroxine sodium.

3. The pharmaceutical solution of claim 2, wherein the EDTA is disodium EDTA.

4. The pharmaceutical solution of claim 3, wherein the solution comprises from 0.05% w/w to 1.0% w/w of the disodium EDTA.

5. The pharmaceutical solution of claim 4, wherein the solution comprises from 80% w/w to 95% w/w of the glycerol.

6. The pharmaceutical solution of claim 5, wherein the solution comprises from 85% w/w of 95% w/w glycerol.

7. The pharmaceutical solution of claim 6, wherein the solution comprises from 90% w/w to 95% w/w glycerol.

8. A pharmaceutical solution comprising:

0.002% w/v, 0.004% w/v, 0.006% w/v, 0.008% w/v, or 0.01% w/v of a levothyroxine;

from 75% w/w to 95% w/w glycerol;

from 0.05% w/w to 1.5% w/w of an EDTA; and

an amount of water sufficient to adjust the pharmaceutical solution to 100% w/w, and

wherein the solution is storage stable.

9. The pharmaceutical solution of claim 8, wherein the levothyroxine is levothyroxine sodium.

10. The pharmaceutical solution of claim 9, wherein the EDTA is disodium EDTA.

11. The pharmaceutical solution of claim 10, wherein the solution comprises from 80% w/w to 95% w/w glycerol.

12. The pharmaceutical solution of claim 11, wherein the solution comprises from 85% w/w to 95% w/w glycerol.

13. The pharmaceutical solution of claim 12, wherein the solution comprises from 90% w/w to 95% w/w glycerol.

14. A pharmaceutical solution comprising:

0.002% w/v or 0.004% w/v of a levothyroxine;

from 75% w/w to 95% w/w glycerol;

from 0.05% w/w to 1.0% w/w of an EDTA,

an amount of water sufficient to adjust the pharmaceutical solution to 100% w/w, and

wherein the solution is storage stable.

15. The pharmaceutical solution of claim 14, wherein the solution comprises from 80% w/w to 95% w/w glycerol.

16. The pharmaceutical solution of claim 15, wherein the solution comprises from 85% w/w to 95% w/w glycerol.

17. The pharmaceutical solution of claim 14, wherein the solution comprises from 90% w/w to 95% w/w glycerol.

18. A pharmaceutical solution comprising:

from 0.002% w/v to 0.006% w/w of a levothyroxine sodium;

from 90% w/w to 95% w/w glycerol;

an amount of water sufficient to adjust the pharmaceutical solution to 100% w/w; and

0.08% w/w of an EDTA, and

wherein the solution is storage stable.

19. The pharmaceutical solution of claim 18, wherein the levothyroxine is levothyroxine sodium, and wherein the EDTA is disodium EDTA.