Thyroid hormone formulations

• US 20020077364A1
• Filed: 07/06/2001
• Published: 06/20/2002
• Est. Priority Date: 07/06/2000
• Status: Abandoned Application

• Current Assignee: Delsys Pharmaceutical Corporation (Perrigo Company PLC)
• Original Assignee: Delsys Pharmaceutical Corporation (Perrigo Company PLC)
• Inventors: Chrai, Suggy S., Murari, Ramaswamy
• Application Number:
  US09/900,094
• Publication Number:
  US 20020077364A1
• 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 9/2086 Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat active cores with a complete drug-free outer coat A61K9/28
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4

Abstract

A method is disclosed for formulating a solid dosage of thyroid hormone, while avoiding instability caused by interaction of the active ingredient with excipients. The thyroid hormone may be levothyroxine sodium or triiodothyronine. The method comprises depositing the active ingredient, preferably electrostatically, as a dry powder substantially free of excipients, onto a pharmaceutically acceptable polymer substrate. Solid pharmaceutical dosage forms also are disclosed.

Claims

1. A method of formulating a solid dosage of thyroid hormone, while avoiding instability caused by interaction of the active ingredient with excipients, comprising depositing the active ingredient, as a dry powder substantially free of excipients, onto a pharmaceutically acceptable polymer substrate.

2. The method of claim 1, wherein the depositing is performed electrostatically.

3. The method of claim 1, wherein the thyroid hormone is levothyroxine sodium or triiodothyronine.

4. The method of claim 1, wherein the polymer has received regulatory approval and is of GRAS status.

5. The method of claim 4, wherein the polymer is selected from the group consisting of polyvinyl alcohol, polyvinyl pyrrolidinone, polysaccharide polymers, acrylate polymers, methacrylate polymers, phthalate polymers, polyvinyl acetate, methyl cellulose, carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, ethyl cellulose, Eudragits, starch-based polymers, gelatin, and combinations thereof.

6. The method of claim 4, wherein the polymer is substantially unreactive with an amino group or iodo group in the thyroid hormone molecule.

7. The method of claim 6, wherein the polymer is selected from the group consisting of hydroxypropylcellulose, hydroxypropylmethylcellulose, ethyl cellulose and combinations thereof.

13. The method of claim 2, further comprising:

(a) applying a cover film to encapsulate the electrostatically deposited active ingredient, so as to form a stable core; and

(b) further processing the stable core into a dosage form resembling a tablet, capsule, caplet, wafer or stamp-like presentation.

8. An improved solid pharmaceutical dosage formulation, comprising a therapeutic amount of thyroid hormone, electrostatically deposited on a pharmaceutically acceptable polymer substrate as a dry powder substantially free of excipients, wherein the average powder particle size is less than about 15μ

.

9. The formulation of claim 8, wherein the thyroid hormone is levothyroxine sodium or triiodothyronine.

10. The formulation of claim 8, wherein the average powder particle size is less than about 10μ

.

11. The formulation of claim 8, wherein the average powder particle size is less than about 5μ

.

12. The formulation of claim 8, wherein the polymer is substantially unreactive with an amino group or iodo group in the thyroid hormone molecule.