Formulations having increased stability during transition from hydrophobic vehicle to hydrophilic medium

• US 20050266087A1
• Filed: 05/19/2005
• Published: 12/01/2005
• Est. Priority Date: 05/25/2004
• Status: Abandoned Application

• Current Assignee: Intarcia Therapeutics, Inc.
• Original Assignee: Intarcia Therapeutics, Inc.
• Inventors: DesJardin, Michael A., Junnarkar, Gunjan, Liu, Kui, Li, Zengji
• Application Number:
  US11/132,830
• Publication Number:
  US 20050266087A1
• Time in Patent Office: Days
• US Class Current: 424/488
• CPC Class Codes: A61K 31/7024 Esters of saccharides
• CPC Class Codes: A61K 38/21 Interferons [IFN]
• 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 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1623 Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules

Abstract

A suspension formulation for therapeutic use includes a non-aqueous, hydrophobic vehicle exhibiting viscous fluid characteristics, a dry particle formulation comprising a biomolecule dispersed in the vehicle, and a surfactant incorporated in at least one of the vehicle and dry particle formulation. A dry particle formulation includes an interferon, a buffer, a surfactant, and one or more stabilizers selected from the group consisting of a carbohydrate, an antioxidant, and an amino acid.

Claims

1. A suspension formulation for therapeutic use, comprising:

a non-aqueous, hydrophobic vehicle exhibiting viscous fluid characteristics;

a dry particle formulation comprising a biomolecule dispersed in the vehicle; and

a surfactant incorporated in at least one of the vehicle and dry particle formulation.

2. The suspension formulation of claim 1, wherein the hydrophobic vehicle is non-polymeric.

3. The suspension formulation of claim 2, wherein the hydrophobic vehicle comprises substantially sucrose acetate isobutyrate.

4. The suspension formulation of claim 1, wherein the biomolecule is an interferon.

5. The suspension formulation of claim 4, which delivers the interferon from an implantable drug delivery device at 1 ng/day to 600 μ

g/day over at least one month.

6. The suspension formulation of claim 1, wherein the biomolecule is an interferon omega.

7. The suspension formulation of claim 1, wherein the biomolecule is spray dried with the surfactant.

8. The suspension formulation of claim 1, wherein the dry particle formulation further comprises one or more stabilizers and a buffer.

9. The suspension formulation of claim 8, wherein the stabilizers are selected from the group consisting of carbohydrate, antioxidant, and amino acid.

10. The suspension formulation of claim 1, wherein the hydrophobic vehicle is present in an amount greater than 60 wt %.

11. The suspension formulation of claim 1, wherein the dry particle formulation is present in a range from 0.01 to 40 wt %.

12. The suspension formulation of claim 1, wherein a surfactant loading in the dry particle formulation is in a range from 0 to 10 wt %.

13. The suspension formulation of claim 1, wherein a surfactant loading in the vehicle is in a range from 0 to 20 wt %.

14. A dry particle formulation comprising:

an interferon, a buffer, a surfactant, and one or more stabilizers selected from the group consisting of a carbohydrate, an antioxidant, and an amino acid.

15. The dry particle formulation of claim 14, which is spray dried.

16. The dry particle formulation of claim 14, wherein the interferon is interferon omega.

17. The dry particle formulation of claim 14, wherein the interferon is present in an amount ranging from 0.1 to 99.9 wt %.

18. The dry particle formulation of claim 17, wherein a weight ratio of each stabilizer to the interferon is in a range from 0.1 to 99.9.

19. The dry particle formulation of claim 18, wherein a weight ratio of each stabilizer to the interferon is greater than 0.5.

20. The dry particle formulation of claim 19, wherein a weight ratio of the carbohydrate to the interferon is greater than 1.0.

21. The dry particle formulation of claim 14, wherein a concentration of the buffer is in a range from 5 mM to 50 mM.

22. The dry particle formulation of claim 14, wherein a pH of the buffer is in a range from 5.0 to 8.0.

23. The dry particle formulation of claim 14, wherein interferon, carbohydrate, antioxidant and/or amino acid, buffer, and surfactant are present in a ratio of 1:

2;

1;

1.5-2.5;

0.06.

24. The dry particle formulation of claim 14, wherein the interferon is interferon omega, the carbohydrate is sucrose, the antioxidant and/or amino acid is methionine, and the buffer is citrate.

25. The dry particle formulation of claim 14, wherein the surfactant is present in a range from 0.01 to 10 wt %.

26. The dry particle formulation of claim 14, wherein the surfactant is present in a range from 0.01 to 5 wt %.

27. An implantable delivery device comprising:

a suspension formulation comprising a non-aqueous, hydrophobic vehicle exhibiting viscous fluid characteristics, a dry particle formulation comprising an interferon dispersed in the vehicle, and a surfactant incorporated in at least one of the vehicle and dry particle formulation; and

a reservoir containing the suspension formulation in an amount sufficient to provide continuous delivery of the interferon in a therapeutically effective dose in an environment of use over at least one month.

28. A method of enhancing release of interferon omega in a hydrophilic release rate medium, comprising:

suspending a dry particle formulation of interferon omega in a non-polymeric, hydrophobic vehicle; and

incorporating a surfactant in at least one of the dry particle formulation and the hydrophobic vehicle.