Stable dosage of levothyroxine sodium and process of production

• US 5,225,204 A
• Filed: 11/05/1991
• Issued: 07/06/1993
• Est. Priority Date: 11/05/1991
• Status: Expired due to Term

• Current Assignee: Knoll BV (BASF SE)
• Original Assignee: Dimitri C. Papadimitriou, Jivn-Ren Chen
• Inventors: Papadimitriou, Dimitri C., Chen, Jivn-Ren
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): Hulina, Amy
• Application Number:
  US07/787,829
• Time in Patent Office: 609 Days
• Field of Search: 424/451, 424/464, 424/486, 424/488
• US Class Current: 424/484
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds

Abstract

A stable dosage form of levothyroxine sodium which includes a stable complex of levothyroxine sodium and a cellulose compound, polyvinylpyrrolidone or a Poloxamer, which complex is adsorbed on the surface of a cellulose compound carrier. In a first embodiment the stable complex of levothyroxine sodium is prepared by mixing the levothyroxine sodium with a complexing agent such as polyvinylpyrrolidone or a Poloxamer, dissolving the resulting mixture in a polar organic solvent such as water, methanol, ethanol, propanol, isopropyl alcohol, methylene dichloride or butanol, adding a cellulose carrier to the liquid and subsequently drying the resulting mixture to obtain a powdery, stabilized complex of levothyroxine sodium and polyvinylpyrrolidone or Poloxamer adsorbed on the cellulose carrier. In a second embodiment the levothyroxine sodium is at least partially dissolved directly in the polar organic solvent and a cellulose carrier is added to the solution to produce the stabilized levothyroxine sodium complex. In a third embodiment the levothyroxine sodium is dry mixed with a cellulose complexing agent and a cellulose carrier to produce the stabilized levothyroxine sodium complex. The complexes can be mixed with pharmaceutically acceptable excipients for compression into tablets or placed in capsules to define stable levothyroxine sodium dosage formulations.

Claims

1. A stabilized and uniform pharmaceutical formulation of Levothyroxine sodium comprising a complex of Levothyroxine sodium and a water soluble polyvinylpyrrolidone adsorbed on a cellulose compound in the form of a tablet, powder or capsule.

2. The stabilized and uniform pharmaceutical formulation of claim 1 wherein said polyvinylpyrrolidone is linear N-vinyl-2-pyrrolidone.

3. The stabilized and uniform pharmaceutical formulation of claim 1, wherein said cellulose compound is selected from the group, microcrystalline cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, low substituted hydroxypropyl cellulose and hydroxypropylmethyl cellulose.

4. The stabilized and uniform pharmaceutical formulation of claim 1 wherein:

(a) said polyvinylpyrrolidone is linear N-vinyl-2-pyrrolidone; and

(b) said cellulose compound is selected from the group, microcrystalline cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, low substituted hydroxypropyl cellulose and hydroxypropylmethyl cellulose.

9. The stabilized pharmaceutical formulation of claim 1 further comprising at least one pharmaceutically acceptable excipient mixed with said complex and said cellulose compound to define a stabilized pharmaceutical levothyroxine sodium dosage formulation.

10. The stabilized pharmaceutical formulation of claim 9 wherein said excipient comprises at least one of a diluent, a disintegration agent, a glidant and a lubricant.

5. A stabilized and uniform pharmaceutical formulation of levothyroxine sodium comprising a complex of levothyroxine sodium and a block copolymer of ethylene oxide and propylene oxide adsorbed on a cellulose compound in the form of a tablet, powder or capsule.

6. The stabilized uniform pharmaceutical formulation of claim 5 wherein said cellulose compound is selected from the group, microcrystalline cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, low substituted hydroxypropyl cellulose and hydroxypropylmethyl cellulose.

11. The stabilized pharmaceutical formulation of claim 5 further comprising at least one pharmaceutically acceptable excipient mixed with said complex and said cellulose compound to define a stabilized pharmaceutical levothyroxine sodium dosage formulation.

12. The stabilized pharmaceutical formulation of claim 11 wherein said excipient comprises at lest one of a diluent, a disintegration agent, a glidant and a lubricant.

7. A stabilized pharmaceutical formulation of levothyroxine sodium comprising levothyroxine sodium substantially uniformly adsorbed on a cellulose compound in the form of a tablet, powder or capsule.

8. The stabilized pharmaceutical formulation of claim 7 wherein said cellulose compound is selected from the group microcrystalline cellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, low substituted hydroxypropyl cellulose and hydroxypropylmethyl cellulose.

13. The stabilized pharmaceutical formulation of claim 7 further comprising at least one pharmaceutically acceptable excipient mixed with said levothyroxine sodium and said cellulose compound to define a stabilized pharmaceutical levothyroxine sodium dosage formulation.

14. The stabilized formulation of claim 13 wherein said excipient comprises at least one of a diluent, a disintegration agent, a glidant and a lubricant.