Stable pharmaceutical compositions of thyroid hormone drug

• US 9,682,045 B2
• Filed: 11/20/2015
• Issued: 06/20/2017
• Est. Priority Date: 11/21/2014
• Status: Active Grant

• Current Assignee: Cadila Healthcare Limited (Zydus Lifesciences Limited)
• Original Assignee: Cadila Healthcare Limited (Zydus Lifesciences Limited)
• Inventors: Kannan, Muthaiyyan Essakimuthu, Pandya, Nitesh Nalinchandra, Patel, Chetan Kacharabhai
• Primary Examiner(s): SHIAO, REI TSANG
• Application Number:
  US14/946,947
• Publication Number:
  US 20160143855A1
• Time in Patent Office: 578 Days
• Field of Search: 514567
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• 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 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• 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: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets

Abstract

The present invention relates to pharmaceutical compositions comprising a thyroid hormone drug. The invention also relates to processes for the preparation of such compositions.

Claims

1. A stable oral pharmaceutical composition comprising levothyroxine sodium, one or more carbohydrates selected from the group consisting of isomalt, arabinose, dextrose, sucrose, fructose, maltose and trehalose, and one or more pharmaceutically acceptable excipients, wherein the composition retains at least 95% of the potency of levothyroxine sodium after storage for 24 months at 25°

C. and 75% relative humidity.

2. The stable oral pharmaceutical composition according to claim 1, wherein the composition comprises from about 1 to about 95% by weight of the carbohydrates based on the total weight of the composition.

3. The stable oral pharmaceutical composition according to claim 1, wherein the carbohydrate is isomalt.

4. The stable oral pharmaceutical composition according to claim 3, wherein the stable composition comprises about 75% by weight of isomalt based on the total weight of the composition.

5. The stable oral pharmaceutical composition according to claim 1, wherein the composition is a tablet.

6. The stable oral pharmaceutical composition according to claim 1, wherein the pharmaceutically acceptable excipients comprise one or more of diluents, binders, lubricants, surfactants, disintegrants, and antioxidants.

7. The stable oral pharmaceutical composition according to claim 1, wherein the composition is prepared by a wet granulation process.

8. The stable oral pharmaceutical composition according to claim 7, wherein the wet granulation process comprises the following steps:

a) blending one or more carbohydrates, diluents and binders together;

b) dissolving or dispersing a levothyroxine sodium and an antioxidant in a granulating fluid, optionally including a surfactant;

c) granulating the blend of step (a) with the solution/dispersion of step (b);

d) drying and sizing the granules;

e) mixing the sized granules with one or more carbohydrates, disintegrants, lubricants and optionally diluents; and

f) preparing the pharmaceutical composition comprising the granule blend of step (e).

9. The stable oral pharmaceutical tablet composition according to claim 5 having a break-line, wherein the break-line allows the tablet to be divided in two equal parts having substantially equal amounts of the levothyroxine sodium.

10. The stable oral pharmaceutical composition according to claim 9, wherein the tablet composition comprises one or more carbohydrates and one or more pharmaceutically acceptable excipients.

11. The stable oral pharmaceutical composition according to claim 10, wherein the tablet composition comprises from about 1 to about 95% by weight of the carbohydrates based on the total weight of the composition.

12. The stable oral pharmaceutical composition according to claim 10, wherein the pharmaceutically acceptable excipients comprise one or more diluents, binders, lubricants, surfactants, disintegrants, and antioxidants.

13. The stable oral pharmaceutical composition comprising according to claim 1, wherein the composition does not contain more than 1% w/w of total impurities after storage for 3 months at 40°

C./75% relative humidity.

14. The stable oral pharmaceutical composition according to claim 1, wherein the composition does not contain more than 0.3% w/w of related impurity tetraiodothyroacetic acid after storage for 3 months at 40°

C./75% relative humidity.