Stabilized thyroid hormone preparations and methods of making same

• US 6,056,975 A
• Filed: 09/18/1998
• Issued: 05/02/2000
• Est. Priority Date: 11/14/1995
• Status: Expired due to Term

• Current Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated)
• Original Assignee: BASF Corporation (BASF SE)
• Inventors: Srinivas, Raghunath, Mitra, Amit K., Thomas, Charles L. III
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): HOWARD, SHARON LEE
• Application Number:
  US09/156,844
• Time in Patent Office: 592 Days
• Field of Search: 424/464, 424/465, 424/479, 424/480
• US Class Current: 424/464
• 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 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4

Abstract

Disclosed are thyroid hormone preparations useful in pharmaceutical applications. These preparations are disclosed to contain thyroxine drugs in combination with an inorganic salt, a carbohydrate having a molecular weight of greater than 500, and glycine. The preparations are also disclosed to have a free water content less than 4.5% by weight of the preparation. Also provided are compositions containing a reduced carbohydrate, a water soluble polysaccharide, or galactose. The preparations have improved stability wherein they are provided as being stable to the extent that substantially no potency loss is measured when the preparation is stored at 40° C. and 75% relative humidity for 3 months.

Claims

1. A stable, solid dosage form pharmaceutical preparation suitable for the treatment of thyroid disorders, said preparation comprising:

an effective amount of a thryoxine drug; and

a water soluble glucose polymer;

said preparation being stable to the extent that substantially no potency loss is measured when the preparation is stored at 40°

C. and 75% relative humidity for 3 months.

2. The preparation of claim 1, wherein the preparation is in a unit dose form.

3. The preparation of claim 2, wherein the unit dose form is a tablet.

4. The preparation of claim 3, wherein the tablet additionally includes a lubricant and a binder.

5. The preparation of claim 4, wherein the tablet also contains a glidant.

6. The preparation of claim 2, wherein the unit dose form is a capsule.

7. The preparation of claim 1, wherein the capsule also contain a lubricant and a glidant.

8. The preparation of claim 1, wherein the preparation is in the form of a powder.

9. The preparation of claim 1, wherein the polymer is selected from the group consisting of maltodextrin, β

-cyclodextrin and hydroxypropyl-β

-cyclodextrin.

10. The preparation of claim 1 wherein the pH of the preparation is about 7 to 11.

11. The preparation of claim 1 wherein the thyroxine drug is levothyroxine sodium.

12. The preparation of claim 1 wherein the preparation contains less than 5% by weight of the total of lactose, glucose and sucrose.

13. The preparation of claim 12 wherein the preparation contains substantially no lactose, glucose or sucrose.

14. Preparation of claim 1, wherein the preparation, when stored at 40°

C. and 75% RH for 3 months, exhibits less than 10% by weight loss of the thyroxine drug.

15. A stable pharmaceutical composition comprising:

a. an effective amount of a thyroxine drug;

b. a water soluble polysaccharide; and

c. a free water content less than 4.5% by weight of the preparation, wherein the pH of the composition has a pH greater than about 7.

16. The composition of claim 15 wherein the water-soluble polysaccharide is polysaccharide having a dextrose value of less than 25.

17. The composition of claim 15 wherein the water soluble polysaccharide is a polysaccharide having a dextrose value of less than 10.

18. The composition of claim 15 wherein the water soluble polysaccharide comprises a polysaccharide selected from group consisting of maltodextrin, β

cyclodextrin, and hydroxypropyl-β

-cyclodextrin.

19. The composition of claim 15, wherein the preparation is a unit dose form.

20. The composition of claim 16, wherein the preparation is a unit dose form.

21. The composition of claim 17, wherein the preparation is a unit dose form.

22. The composition of claim 18, wherein the preparation is a unit dose form.

23. The composition of claim 19, wherein the unit dose form is a tablet.

24. The composition of claim 20, wherein the unit dose form is a tablet.

25. The composition of claim 21, wherein the unit dose form is a tablet.

26. The composition of claim 22, wherein the unit dose form is a tablet.

27. The composition of claim 23, wherein the tablet additionally includes a lubricant and a binder.

28. The composition of claim 24, wherein the tablet additionally includes a lubricant and a binder.

29. The composition of claim 25, wherein the tablet additionally includes a lubricant and a binder.

30. The composition of claim 26, wherein the tablet additionally includes a lubricant and a binder.

31. The preparation of claim 23, wherein the tablet also contains a glidant.

32. The preparation of claim 24, wherein the tablet also contains a glidant.

33. The preparation of claim 25, wherein the tablet also contains a glidant.

34. The preparation of claim 26, wherein the tablet also contains a glidant.

35. The preparation of claim 27, wherein the tablet also contains a glidant.

36. The preparation of claim 28, wherein the tablet also contains a glidant.

37. The preparation of claim 29, wherein the tablet also contains a glidant.

38. The preparation of claim 30, wherein the tablet also contains a glidant.