Pharmaceutical formulation comprising levothyroxine sodium

• US 20070110803A1
• Filed: 07/08/2004
• Published: 05/17/2007
• Est. Priority Date: 07/10/2003
• Status: Active Grant

• Current Assignee: Aspen Global Incorporated (Aspen Pharmacare Holdings Limited)
• Original Assignee: Glaxo Group Limited (GSK plc)
• Inventors: Krohn, Heiner, Roman, Wanda, Konieczna, Malgorzata, Schlehahn, Henrik, Strozyk, Malgorzata
• Granted Patent: US 7,955,621 B2
• Time in Patent Office: Days
• US Class Current: 424/465
• 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 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 5/18 of the parathyroid hormones

Abstract

There is provided a stable pharmaceutical formulation comprising (a) an effective amount of levothyroxine sodium, (b) microcrystalline cellulose which has a mean particle size of less than 125 μm and is present in an amount of 60 to 85% w/w based upon the total weight of the formulation, and (c) pregelatinised starch present in an amount of 5 to 30% w/w based upon total weight of the formulation. There is also provided a process for the preparation of such a formulation.

Claims

1. A pharmaceutical formulation comprising:

(a) an effective amount of levothyroxine sodium, (b) microcrystalline cellulose which has a mean particle size of less than 125 μ

m and is present in an amount of 60 to 85% w/w based upon the total weight of the formulation, and (c) pregelatinised starch present in an amount of 5 to 30% w/w based upon total weight of the formulation.

2. The pharmaceutical formulation as claimed in claim 1 wherein the microcrystalline cellulose has a mean particle size less than or equal to 100 μ

m.

3. The pharmaceutical formulation as claimed in claim 2 wherein the ratio of microcrystalline cellulose:

pregelatinised starch is in the range of 2;

1 to 15;

1.

4. The pharmaceutical composition as claimed in claim 3 wherein the microcrystalline cellulose and pregelatinised starch comprise water which is present in an amount 3-6% w/w based on the total weight of the formulation.

5. The pharmaceutical formulation as claimed in claim 1 wherein the levothyroxine sodium is hydrated.

6. The pharmaceutical formulation as claimed in claim 5 wherein the levothyroxine sodium is the pentahydrate form.

7. The pharmaceutical formulation as claimed in claim 1 which further comprises one or more glidant/lubricants.

8. The pharmaceutical formulation as claimed in claim 7 wherein the glidant/lubricants are selected from the group consisting of colloidal anhydrous silica, talc, magnesium stearate, and mixtures thereof.

9. The pharmaceutical formulation as claimed in claim 1 which is stable to the extent that potency decreases by less than 5% when the pharmaceutical formulation is stored at 25°

C. and 60% relative humidity for 12 months.

10. The pharmaceutical formulation as claimed in claim 1 in unit dose form.

11. The pharmaceutical formulation as claimed in claim 10 wherein the unit dose form is a tablet.

15. A method of treating thyroid hormone disorders comprising administering a pharmaceutical formulation as claimed in claim 1 to a mammal.

16. A process for preparing a pharmaceutical formulation as claimed in claim 1 comprising (a) preparing a triturate of levothyroxine sodium, (b) mixing the triturate with the remaining components of the pharmaceutical formulation, and (c) compression.

17. The method of claim 15 wherein said mammal is a human.

12. (canceled)

13. (canceled)

14. (canceled)