Pharmaceutical formulations for thyroid hormones

• US 20030050344A1
• Filed: 07/02/2002
• Published: 03/13/2003
• Est. Priority Date: 07/02/2001
• Status: Active Grant

• Current Assignee: Altergon SA
• Original Assignee: Altergon SA
• Inventors: Di Martino, Alessandro, Marchiorri, Maurizio, Mateo Echanagorria, Angel, Garavani, Alberto
• Granted Patent: US 7,723,390 B2
• Time in Patent Office: Days
• US Class Current: 514/567
• 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 38/24 Follicle-stimulating hormone [FSH]; Chorionic gonadotropins, e.g. HCG; Luteinising hormone [LH]; Thyroid-stimulating hormone [TSH]
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• 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 9/485 Inorganic compounds
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4

Abstract

The present invention provides for pharmaceutical formulations based on thyroid hormones enabling a safe and stable oral administration in the framework of the strict therapeutic index prescribed in case of thyroid disorders.

Claims

1. Pharmaceutical composition comprising thyroid hormones or their salts in capsule or in swallowable uniform soft-gel matrices, preferably consisting of gelatin.

2. Composition according to claim 1 in hard capsule.

3. Composition according to claim 1 in soft capsule.

4. Composition according to claim 1, in which thyroid hormones are chosen among T3 and/or T4 or their sodium salts.

5. Composition according to claim 1, in which said capsule or swallowable uniform soft-gel matrix consists of gelatin of A type or B type, or of methylcellulose, hydroxypropylcellulose or calcium alginate.

6. Pharmaceutical composition according to claim 2, in which said hard capsule comprises thyroid hormones in solid form mixed with usual solid pharmaceutical excipients in form of powder, micropellets or other non-compacted microgranules.

7. Pharmaceutical composition according to claim 6, in which said pharmaceutical excipients are chosen among dicalcium phosphate dihydrate, sodium carboxymethyl starch, microcrystalline cellulose, monohydrate lactose, sodium carboxymethylcellulose, maize starch, magnesium stearate and preservatives agents or their combinations.

8. Pharmaceutical composition according to claim 3, in which said soft capsule comprises thyroid hormones in solid form mixed with common solid pharmaceutical excipients in form of powder, micropellets or other non-compacted microgranules.

9. Pharmaceutical composition according to claim 8, in which said pharmaceutical excipients are chosen among dicalcium phosphate dihydrate, sodium carboxymethyl starch, microcrystalline cellulose, monohydrate lactose, sodium carboxymethylcellulose, maize starch, magnesium stearate and preservatives agents or their combinations.

10. Pharmaceutical composition according to claim 3, in which said soft capsule consists of a shell containing thyroid hormones and possible excipients in a liquid or half-liquid vehicle.

11. Pharmaceutical composition according to claim 10, in which said soft capsule contains an inner phase consisting of a liquid, a half-liquid, a paste, a gel, an emulsion or a suspension comprising the liquid vehicle, thyroid hormones and possible excipients in suspension or solution.

12. Pharmaceutical composition according to claim 11, in which said liquid or half-liquid vehicle is chosen among glycerol, ethanol, polyethylene glycol (particularly with a molecular weight of 200-800), glycofurol (tetrahydrofurfuryl alcohol polyethylene glycol ether;

Sigma T3396), 1,2-propylene glycol, pharmaceutically acceptable oils, or non-ionic surfactants, for instance polysorbates (polysorbate 20 or

     80), or various Tweens®

(i.e. monolaurates, monooleates, monopalmitates, monostearates, polyoxyethylene sorbitane trioleates or tristearates, for instance Tween®

80, Sigma P1754), or among their combinations.

13. Pharmaceutical composition according to claim 12 in which said soft elastic capsule contains a liquid or half-liquid inner phase comprising a vehicle consisting of ethanol, glycerol or of a mixture thereof.

14. Pharmaceutical composition according to claim 12 in which said soft elastic capsule contains an inner phase consisting of a paste or gel comprising gelatin and a liquid or semi-liquid vehicle consisting of ethanol, glycerol or of a mixture thereof.

15. Pharmaceutical composition according to claim 1, in which said swallowable uniform soft-gel matrix comprises glycerol, ethanol or mixtures thereof.

16. Pharmaceutical composition according to claim 1, having an enteric coating enabling the release of thyroid hormones in the small intestine.

17. Pharmaceutical composition according to claim 1, having an outer coating which simplifies ingestion.

18. Pharmaceutical composition according to claim 1, in which the material the capsule or the swallowable uniform soft-gel matrix consists of comprises a plasticizer to control its hardness.

19. Pharmaceutical composition according to claim 18, in which said plasticizer is chosen among glycerol, 1,2-propylene glycol, solutions of sorbitol/sorbitanes or their combinations.