Stabilized pharmaceutical and thyroid hormone compositions and method of preparation

• US 7,067,148 B2
• Filed: 02/15/2002
• Issued: 06/27/2006
• Est. Priority Date: 02/15/2001
• Status: Expired due to Term

• Current Assignee: King Pharmaceuticals Research And Development Incorporated (Pfizer Inc.)
• Original Assignee: King Pharmaceuticals Research And Development Incorporated (Pfizer Inc.)
• Inventors: Gemma, Rocco L., Franz, G. Andrew, Strauss, Elaine A., DiMenna, Philip A.
• Primary Examiner(s): Sheikh, Humera N.
• Application Number:
  US10/076,999
• Publication Number:
  US 20030119911A1
• Time in Patent Office: 1,593 Days
• Field of Search: 514/567, 424/464, 424/465, 424/467
• US Class Current: 424/464
• CPC Class Codes: A61K 31/195 having an amino group
• 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 9/2072 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
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: B01F 25/433 Mixing tubes wherein the shape of the tube influences the mixing, e.g. mixing tubes with varying cross-section or provided with inwardly extending profiles
• CPC Class Codes: B01F 25/4334 Mixers with a converging cross-section
• CPC Class Codes: B01F 25/82 uniting flows of material taken from different parts of a receptacle or from a set of different receptacles

Abstract

A pharmaceutical composition with β-sheet microcrystalline cellulose with improved potency life and methods of preparation therefor. Improved thyroid hormone pharmaceutical compositions comprising 50 weight % or more of β-sheet microcrystalline cellulose.

Claims

1. A pharmaceutical composition in a solid dosage form comprising a thyroid hormone salt and a pharmaceutical filler, wherein said pharmaceutical composition (i) is suitable for oral consumption by a patient, (ii) is substantially free of excipients that can react with or degrade the thyroid hormone salt, and (iii) has a stable shelf life of up to about 18 months, and wherein the thyroid hormone salt loses no more than about 12.6% in potency during shelf life.

2. The pharmaceutical composition of claim 1, wherein said filler is a β

-sheet form of microcrystalline and the β

-sheet form of microcrystalline comprises at least about 50 weight % of said pharmaceutical composition by weight.

3. The pharmaceutical composition of claim 1, wherein the thyroid hormone salt is levothyroxine sodium.

4. The pharmaceutical composition of claim 2, wherein the thyroid hormone salt is levothyroxine sodium.

5. The pharmaceutical composition of claim 1, wherein the thyroid hormone salt is liothyronine sodium.

6. The pharmaceutical composition of claim 2, wherein the thyroid hormone salt is liothyronine sodium.

14. The pharmaceutical composition of claim 1, wherein the thyroid hormone salt is an untreated levothyroxine sodium.

15. The pharmaceutical composition of claim 14, wherein the solid dosage form is a tablet.

16. The pharmaceutical composition of claim 14, wherein the excipient is lactose.

17. The pharmaceutical composition of claim 3, wherein the levothyroxine sodium is an untreated levothyroxine sodium.

18. The pharmaceutical composition of claim 17, wherein the solid dosage form is a tablet.

7. A method of preparing a solid dosage form suitable for oral administration comprised of a thyroid hormone salt, said method comprising blending the thyroid hormone salt and a pharmaceutical filler to form a blend, and forming the solid dosage form from the blend, wherein the thyroid hormone salt loses potency at a rate of no more than about 0.7% per month for a period of time equal to at least about 18 months, wherein said period of time begins on the date in which said solid dosage form is first blended, and wherein said solid dosage form is substantially free of excipients that can react with or degrade the thyroid hormone salt.

8. The method of claim 7, wherein the solid dosage is formed by compressing the blend in a tableting machine.

9. The method of claim 8, wherein the blend is compressed in a ratio of initial volume to final volume from 3.3:

1 to 4.0;

1.

10. The method of claim 7, wherein the thyroid hormone salt comprises levothyroxine sodium.

11. The method of claim 7, wherein the thyroid hormone salt comprises liothyronine sodium.

12. The method of claim 8, wherein the tableting machine further comprises extra deep tablet dies that maintain a free clearance of at least 3.0 mm during filling.

13. The method of claim 12, wherein the tableting machine forms tablets in a shape selected from the group consisting of cylindrical shape and raised violin shape.

19. The pharmaceutical composition of claim 7, wherein the thyroid hormone salt is an untreated levothyroxine sodium.

20. The method of claim 19, wherein the solid dosage form is a tablet.

21. The method of claim 20, wherein the excipient is lactose.

22. The method of claim 10, wherein the levothyroxine sodium is an untreated levothyroxine sodium.

23. The method of claim 22, wherein the solid dosage form is a tablet.

24. The method of claim 23, wherein the excipient is lactose.