Solid pharmaceutical preparation containing levothyroxine and/or liothyronine salts

• US 20070014851A1
• Filed: 05/03/2004
• Published: 01/18/2007
• Est. Priority Date: 05/03/2004
• Status: Active Grant

• Current Assignee: Globopharm Pharmazeutische Produktions-Und HandelsGmbH
• Original Assignee: Globopharm Pharmazeutische Produktions-Und HandelsGmbH
• Inventors: Raneburger, Johannes, Burghart, Kurt, Burghart, Walter
• Granted Patent: US 8,293,272 B2
• Time in Patent Office: Days
• 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 9/1623 Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• 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

Abstract

In a solid pharmaceutical preparation containing water-soluble salts of levothyroxine and/or liothyronine as active ingredients, the water activity of said pharmaceutical preparation is adjusted to values of below 0.4 and, preferably, 0.1 to 0.3, measured at room temperature.

Claims

1. A solid pharmaceutical preparation comprising water-soluble salts of one or more selected from the group consisting of levothyroxine and liothyronine as an active ingredient

wherein water activity of said pharmaceutical preparation is adjusted to values of below 0.4 and above 0.1, measured at room temperature.

2. A pharmaceutical preparation according to claim 1, wherein the water activity of said pharmaceutical preparation is adjusted to values ranging from 0.1 to 0.3, measured at room temperature.

3. A pharmaceutical preparation according to claim 1, wherein a methanolic or ethanolic solution of said active ingredient is homogenously applied on a carrier.

4. A pharmaceutical preparation according to claim 3, wherein the carrier is a water-soluble carrier.

5. A pharmaceutical preparation according to claim 4, wherein mannitol is used as a said water-soluble carrier.

6. A pharmaceutical preparation according to claim 3, wherein the carrier is treated with an amount of EDTA-Na substantially corresponding to a Ca⁺⁺-content of the carrier.

7. A pharmaceutical preparation according to claim 1, wherein the preparation is in the form of tablets and is confectioned with non-hygroscopic adjuvants.

16. A pharmaceutical preparation according to claim 3, wherein said carrier is mixed with starch, guar or granulation aids.

17. A pharmaceutical preparation according to claim 3, wherein the carrier is treated with an amount of EDTA-Na substantially corresponding to a Ca⁺⁺-content of the carrier, and citric acid.

18. A pharmaceutical preparation according to claim 1, wherein the preparation is in the form of tablets and is confectioned in a package with little or no water-vapor permeability.

8. A method for producing a pharmaceutical preparation comprising water-soluble salts of one or more selected from the group consisting of levothyroxine and liothyronine as an active ingredient, wherein water activity of said pharmaceutical preparation is adjusted to values of below 0.4 and above 0.1, measured at room temperature, comprising the steps of:

applying to a carrier of mannitol an alcoholic solution of the active ingredient,

evaporating until a water factor of below 0.4 and above 0.1 has been reached, and

then tableting said preparation.

9. A method according to claim 8, further comprising the step of applying water or an aqueous solution containing EDTA-Na to said carrier, prior to said evaporating step.

10. A method according to claim 8 wherein directly tabletable mannitol is used as said carrier.

11. A method according to claim 8, wherein hydrophobic adjuvants are used as tableting aids.

12. A method according to claim 8, further comprising the step of supplementing the carrier with EDTA-Na in an amount sufficient for complexing present bivalent ions, prior to applying the alcoholic solution of the active ingredient.

13. A method according to claim 12, further comprising the step of wetting the carrier with methanol, prior to supplementing the carrier with EDTA-Na.

14. A method according to claim 8, wherein the preparation is kept free of hygroscopic adjuvants.

15. A method according to claim 8, wherein the preparation comprises hygroscopic adjuvants, and is packed in a water-vapor-tight package.

19. A method according to claim 8, wherein the preparation is evaporated until a water factor of below 0.3 and above 0.1 has been reached.

20. A method according to claim 8, further comprising the step of applying water or an aqueous solution containing EDTA-Na and citric acid to said carrier, prior to said evaporating step.

21. A method according to claim 8, wherein hydrophobic adjuvants are used as lubricants.

22. A method according to claim 8, wherein magnesium stearate is used as a tableting aid.

23. A method according to claim 8, further comprising the step of supplementing the carrier with EDTA-Na and citric acid, in an amount sufficient for complexing present bivalent ions, prior to applying the alcoholic solution of the active ingredient.

24. A method according to claim 23, further comprising the step of wetting the carrier with methanol, prior to supplementing the carrier with EDTA-Na and citric acid.