FORMULATIONS FOR AMYLIN AGONIST PEPTIDES

• US 20090018053A1
• Filed: 12/20/2007
• Published: 01/15/2009
• Est. Priority Date: 01/09/1998
• Status: Abandoned Application

• Current Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Inventors: L'ITALIEN, James L., STETSKO, Gregg
• Application Number:
  US11/962,034
• Publication Number:
  US 20090018053A1
• Time in Patent Office: Days
• US Class Current: 514/1.100
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

The present invention is concerned with a pharmaceutical formulation comprising an amylin agonist and optionally a buffer, a tonicifier or stabilizer, and a preservative in a container, for example, a vial, prefilled cartridge, prefilled syringe or disposable pen. This formulation may be in liquid, gel, solid or powdered form for delivery, for example, via nasal, pulmonary, oral, sublingual, buccal, transdermal, or parenteral routes. Formulation with biocompatible polymers and release modifiers, such as sugars, can facilitate controlled release after injection, minimizing the number of administrations to a patient. These formulations maintain stability upon storage under refrigerated or room temperature conditions. Such formulations can be further combined with insulin for administration to a patient.

Claims

1. A liquid pharmaceutical formulation comprising about 0.5 to 1.0% (w/v) of an amylin agonist, a pharmaceutically acceptable excipient, and about 0.005% to 1.0% (w/v) of a preservative.

2. The liquid pharmaceutical formulation according to claim 1, wherein said amylin agonist is pramlintide.

3. The liquid pharmaceutical formulation according to claim 1, further comprising insulin.

4. The liquid pharmaceutical formulation according to claim 3, wherein said insulin is glargine.

5. The liquid pharmaceutical formulation according to claim 1 wherein said preservative is selected from the group consisting of m-cresol, benzyl alcohol, ethyl, ethyl, propyl and butyl parabens and phenol.

6. The liquid pharmaceutical formulation according to claim 1, wherein said preservative is between about 0.1 to 0.3% (w/v) of m-cresol.

7. The liquid pharmaceutical formulation according to claim 1, wherein said preservative is at least 0.15% (w/v) of m-cresol.

8. The liquid pharmaceutical formulation according to claim 1, wherein said amylin agonist is stable for at least 30 days at room temperature.

9. The liquid pharmaceutical formulation according to claim 8, wherein said amylin agonist is pramlintide.

10. A liquid pharmaceutical formulation comprising about 0.5 to 1.0% (w/v) of an amylin agonist, a pharmaceutically acceptable excipient, and insulin.

11. The liquid pharmaceutical formulation according to claim 10, wherein said amylin agonist is pramlintide.

12. The liquid pharmaceutical formulation according to claim 10, wherein said insulin is glargine.

13. A formulation comprising about 1% to 98% (w/w) of an amylin agonist and about 1.0% to 20% (w/w) of at least one pharmaceutically acceptable excipient selected from the group consisting of a preservative, a penetration enhancer and a stabilizer.

14. The formulation according to claim 13 comprising about 80% to 90% (w/w) of said amylin agonist and about 10% to 20% (w/w) of said at least one pharmaceutically acceptable excipient.

15. The formulation according to claim 13 for oral administration, wherein said formulation is solid, wherein said pharmaceutically acceptable excipient is powdered, wherein said pharmaceutically acceptable excipient comprises about 1.0 to 20% (w/w) of said formulation, wherein said formulation comprises a penetration enhancer or stabilizer.

16. The formulation according to claim 15 wherein said formulation is encapsulated within a polymeric coating.

17. The formulation according to claim 15, wherein said powdered excipient is lactose.

18. The formulation according to claim 15, wherein said formulation comprises glargine.

19. The formulation according to claim 13, wherein said amylin agonist is pramlintide.

20. The formulation according to claim 13 which is a solid, liquid, gel or semi-solid.

21. The formulation according to claim 13 which is lyophilized.

22. The formulation according to claim 13, further comprising insulin.

23. The formulation according to claim 22, wherein said insulin is glargine.

24. The formulation according to claim 13 for nasal, pulmonary or buccal delivery.

25. The formulation according to claim 24 comprising a penetration enhancer, or a stabilizer.

26. The formulation according to claim 24 further comprising a polymer.

27. The formulation according to claim 24 further comprising a preservative.

28. The formulation according to claim 13 for administration to a subject, wherein said formulation is administered in the form selected from the group consisting of oral delivery, a microcapsule delivery, a microsphere, an implant delivery, and a polymer matrix delivery.

29. The formulation according to claim 13 formulated in tablets or capsules for oral, sublingual or buccal delivery.

30. The formulation according to claim 13 formulated in powder form for nasal or pulmonary delivery.

31. The formulation according to claim 13 formulated for transdermal delivery.

32. A method for treating diabetes in a patient in need of such treatment comprising administering a therapeutically effective amount of the formulation according to claim 14 to the patient in need of such treatment.

33. The method according to claim 32 wherein insulin is admixed with said formulation.

34. The method according to claim 33 wherein said admixing step is simultaneous, or concerted and sequential.

35. A liquid suspension formulation comprising about 0.5 to 90% (w/v) of an amylin agonist, insulin, about 1.0 to 10% (w/v) of a carbohydrate or a polyhydric alcohol, and about 0.02 to 0.5% (w/v) of an acetate, phosphate, citrate or glutamate buffer, and a liquid vehicle, wherein the formulation has a pH of about 3.5 to 5.0.

36. The formulation according to claim 35, wherein said amylin agonist is pramlintide.

37. The formulation according to claim 35, wherein said insulin is glargine.