SOLID PHARMACEUTICAL PREPARATION CONTAINING LEVOTHYROXINE

• US 20150231101A1
• Filed: 08/01/2013
• Published: 08/20/2015
• Est. Priority Date: 08/20/2012
• Status: Abandoned Application

• Current Assignee: Merck Patent GmbH (Merck & Co., Inc.)
• Original Assignee: Merck Patent GmbH (Merck & Co., Inc.)
• Inventors: Lindenblatt, Hiltrud, Frank, Thomas T., Vonderschmitt, Reiner
• Application Number:
  US14/422,546
• Publication Number:
  US 20150231101A1
• Time in Patent Office: Days
• US Class Current: 1/1
• 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 47/12 Carboxylic acids; Salts or anhydrides thereof
• 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 9/1658 Proteins, e.g. albumin, gelatin
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/28 Dragees; Coated pills or tablets , e.g. with film or compression coating A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/50 Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals A61K9/2081 takes precedence; particles with a single coating comprising drug A61K9/167
• 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

The invention relates to a solid pharmaceutical preparation comprising levothyroxine sodium, gelatine, citric acid and a filler. The solid pharmaceutical preparation has an improved stability.

Claims

1. Solid pharmaceutical preparation comprising levothyroxine sodium, gelatine, citric acid and a filler.

2. Solid pharmaceutical preparation according to claim 1, characterized in that it comprises liothyronine sodium.

3. Solid pharmaceutical preparation according to claim 1, characterized in that the filler is a sugar alcohol such as sorbitol or mannitol dulcitol, xylitol or ribitol, preferably sorbitol or mannitol, particular preferably mannitol, a sugar such as glucose, fructose, mannose, lactose, saccharose or maltose, preferably lactose, saccharose or maltose, particular preferably lactose, a starch such as potato starch, rice starch, maize starch or pregelatinized starch, preferably maize starch or pregelatinized starch, particular preferably maize starch, a cellulose such as powdered cellulose or microcrystalline cellulose, preferably microcrystalline cellulose, or a mixture thereof.

4. Solid pharmaceutical preparation according to claim 3, characterised in that the filler is mannitol and/or maize starch.

5. Solid pharmaceutical preparation according to claim 1, characterized in that it further comprises an antioxidant selected from the group consisting of tocopherol, propyl gallate, tertiary butylhydroquinone, butylated hydroxyanisole and butylated hydroxytoluene, preferably hydroxyanisole or butylated hydroxytoluene, particular preferably butylated hydroxytoluene.

6. Solid pharmaceutical preparation according to claim 1, characterised in that it is in granule, pellet, capsule or tablet form.

7. Solid pharmaceutical preparation according to claim 6, characterised in that it is a tablet.

8. Solid pharmaceutical preparation according to claim 1, characterised in that at least one disintegrating agent is present.

9. Solid pharmaceutical preparation according to claim 8, characterized in that the disintegrating agent is sodium starch glycolate, or carboxymethylcellulose sodium or a mixture thereof.

10. Solid pharmaceutical preparation according to claim 9, characterized in that the disintegrating agent present is carboxymethylcellulose sodium.

11. Solid pharmaceutical preparation according to claim 1, characterised in that it comprises 1 to 10% by weight of gelatine, 0.1 to 3% by weight citric acid, 50 to 80% by weight of mannitol or lactose, 10 to 30% by weight maize starch.

12. Solid pharmaceutical preparation according to claim 11, characterised in that it comprises 0.05 to 0.5% by weight butylated hydroxytoluene.

13. Process for the production of a solid pharmaceutical preparation according to claim 7, characterized in that

(a) levothyroxine sodium and optionally liothyronine sodium is/are suspended in an aqueous gelatine solution,

(b) the suspension obtained by step (a) is sprayed onto the filler in a fluidized bed granulation and dried to form granules,

(c) the granules obtained by step (b) is collected and optionally,

(d) a disintegrant and optionally a lubricant is/are mixed with the granules obtained by step (c), and

(e) the mixture obtained by step (d) is compressed to give tablets.

14. Process for the production of a solid pharmaceutical preparation according to claim 13, characterized in that citric acid and, if present, the antioxidant is dissolved in the aqueous gelatine solution used in step (a) or is admixed with the granules in step (d).

15. Process for the preparation of a solid pharmaceutical preparation according to claim 13, characterised in that the granules or the tablets are provided with a coating.