Levothyroxine compositions having unique triiodothyronine Tmax properties

• US 20030190359A1
• Filed: 10/29/2002
• Published: 10/09/2003
• Est. Priority Date: 10/29/2001
• Status: Abandoned Application

• Current Assignee: Elaine A. Strauss, Franz G. Andrew, Philip A. Dimenna, Rocco L. Gemma
• Original Assignee: Elaine A. Strauss, Franz G. Andrew, Philip A. Dimenna, Rocco L. Gemma
• Inventors: Gemma, Rocco L., Franz, G. Andrew, Strauss, Elaine A., DiMenna, Philip A.
• Application Number:
  US10/282,703
• Publication Number:
  US 20030190359A1
• Time in Patent Office: Days
• US Class Current: 424/468
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2072 characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms A61K9/0004, A61K9/0056, A61K9/0065 take precedence

Abstract

The present invention generally relates to stable pharmaceutical compositions, and methods of making and administering such compositions. In one aspect, the invention features stabilized pharmaceutical compositions that include pharmaceutically active ingredients such as levothyroxine (T4) sodium and liothyronine (T3) sodium (thyroid hormone drugs), preferably in an immediate release solid dosage form. Also provided are methods for making and using such immediate release and stabilized compositions.

Claims

1. A stabilized pharmaceutical composition in solid dosage form comprised of a levothyroxine salt and a stabilizing agent.

2. A composition of claim 1, wherein at least about 85% of the levothyroxine dissolves in aqueous solution in less than about 20 minutes as determined by a standard dissolution test.

3. A composition of claim 1, wherein at least about 80% of the levothyroxine dissolves in aqueous solution by about 15 minutes as determined by the standard dissolution test.

4. A composition of claims 1-3, wherein the composition has a post-packaging potency of between from about 95% to about 120% as determined by a standard potency test.

5. A composition of claim 1-3, wherein the composition has a post-packaging potency of between from about 98% to about 110% as determined by the standard potency test.

6. A composition of claims 1-3, wherein the composition is formulated as a tablet.

7. A composition of claim 6, wherein the tablet is configured to increase heat transfer away from the tablet.

8. A composition of claim 6-7, wherein the tablet has a surface area of between from about 0.9 in.2 to about 0.15 in.2

9. A composition of claims 6-8, wherein the tablet is beveled.

10. A composition of claims 6-9, wherein the tablet is scored.

11. A composition of claims 6-10, wherein the tablet is in a shape selected from the group consisting of cylindrical shape and raised violin shape.

12. A composition of claims 1-11, wherein the composition comprises between from about 0.01 mg/tablet to about 500 mg/tablet levothyroxine sodium (USP).

13. A composition of claims 1-11, wherein the stabilizing agent is a β

-sheet form of microcrystalline cellulose.

14. A composition of claim 1-13, wherein the stabilizing agent used is at least about 50 weight % of the composition weight.

15. A composition of claim 1-13, wherein the stabilizing agent used is in the range of is in the range of about 50 weight % to about 99 weight % of the composition.

16. A composition of claim 1-13, wherein the stabilizing agent used is in the range of is in the range of about 60 weight % to about 90 weight % of the composition.

17. A composition of claim 13-16, wherein the microcrystalline β

-cellulose has a bulk density of between from about 0.10 g/cm3 to about 0.35 g/cm3.

18. The composition of claims 13-16, wherein the microcrystalline β

-cellulose has a bulk density of between from about 0.15 g/cm3 to about 0.25 g/cm3.

19. The composition of claims 13-16, wherein the microcrystalline β

-cellulose has a bulk density of between from about 0.17 g/cm3 to about 0.23 g/cm3.

20. A composition of claims 13-16, wherein the microcrystalline β

-cellulose has a bulk density of between from about 0.19 g/cm3 to about 0.21 g/cm3.

21. A composition of claims 13-20, wherein the microcrystalline β

-cellulose has a conductivity of less than about 200 μ

S/cm.

22. A composition of claim 13-20, wherein the microcrystalline β

-cellulose has a conductivity of less than about 75 μ

S/cm.

23. A composition of claims 13-20, wherein the microcrystalline β

-cellulose has a conductivity of between from about 0.5 μ

S/cm to 50 μ

S/cm.

24. A composition of claims 13-20, wherein the microcrystalline β

-cellulose has a conductivity of between from about 15 μ

S/cm to 30 μ

S/cm.

25. A composition of claims 13-24, wherein the microcrystalline β

-cellulose is marketed under the trademark Ceolus KG-801 or KG-802.

26. A composition of claims 13-25, wherein the microcrystalline β

-cellulose is flat needle shaped.