Thyroxine/cyclodextrin complexes and pharmaceutical compositions containing the same

• US 5,856,359 A
• Filed: 07/24/1997
• Issued: 01/05/1999
• Est. Priority Date: 11/29/1995
• Status: Expired due to Fees

• Current Assignee: Hexal AG (Novartis Ag)
• Original Assignee: Hexal AG (Novartis Ag)
• Inventors: Bracher, Daniel, Fischer, Wilfried
• Primary Examiner(s): HENLEY III, RAYMOND J
• Application Number:
  US08/875,366
• Time in Patent Office: 530 Days
• Field of Search: 514/58, 514/567
• 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 47/6951 using cyclodextrin cyclodextrins used as simple excipients A61K47/40
• CPC Class Codes: A61K 9/7061 Polyacrylates
• CPC Class Codes: A61K 9/7084 Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

Thyroxine containing pharmaceutical compositions with improved aqueous solubility, stability and enhanced membrane permeation have been prepared by formulating thyroxine with cyclodextrins. These thyroxine/cyclodextrin complexes can further be transformed into different dosage forms (oral tablets, injectables, transdermal patches, hydrogels, ointments, suppositories etc.) by employing known, common pharmaceutical additives.

Claims

1. A transdermal composition comprising a solution or hydrogel of γ

-cyclodextrin and a thyroxine selected from the group consisting of L-thyroxine, D-thyroxine, a pharmaceutically acceptable salt of L-thyroxine, a pharmaceutically acceptable salt of D-thyroxine, and mixtures thereof.

2. The composition of claim 1 wherein said pharmaceutically acceptable salt is a sodium salt.

3. The composition of claim 1 wherein said thyroxine is a free acid of D-thyroxine or L-thyroxine.

4. The composition of claim 1 wherein the molar ratio of γ

-cyclodextrin to thyroxine is from about 25;

1 to about 0.5;

1.

5. The composition of claim 4 wherein said molar ratio is from about 4:

1 to 1;

1.

6. The composition of claim 1 wherein said thyroxine comprises L-thyroxine sodium.

7. A process for the preparation of a composition according to claim 1, comprising kneading said γ

-cyclodextrin with said thyroxine in the presence of water.

8. The process of claim 7 wherein said water is present in an amount corresponding to the amount of water necessary to solubilize said composition up to twice that amount of water.

9. A pharmaceutically active thyroxine preparation comprising the composition of claim 1.

10. The pharmaceutically active thyroxine preparation of claim 9 further comprising adjuvants and auxiliary agents suitable for a composition to be administered by an transdermal administration method.

11. The pharmaceutically active thyroxine preparation of claim 10 comprising a reservoir containing a hydrogel having said thyroxin composition therein.

12. The pharmaceutically active thyroxine preparation of claim 9 further comprising at least one gelling agent selected from the group consisting of a polyacrylic acid, a polyacrylic acid derivative, and mixtures thereof.

13. A method of administering a thyroxine to a patient in need thereof, comprising administering to said patient the composition of claim 1.

14. The method of claim 13 wherein said composition is in the form of a transdermal patch.

15. The method of claim 13 wherein said composition comprises γ

-cyclodextrin and a thyroxine selected from the group consisting of L-thyroxin, pharmaceutically acceptable salts of L-thyroxin, and mixtures thereof.

16. The transdermal composition of claim 1 wherein said thyroxine is a pharmaceutically acceptable alkali metal salt of D-thyroxine, a pharmaceutically acceptable alkali metal salt of L-thyroxine, or a mixture or racemate thereof.