Polyoxaester suspending vehicles for use with implantable delivery systems

• US 8,114,430 B2
• Filed: 05/03/2011
• Issued: 02/14/2012
• Est. Priority Date: 03/15/2005
• Status: Active Grant

• Current Assignee: Intarcia Therapeutics, Inc.
• Original Assignee: Intarcia Therapeutics, Inc.
• Inventors: Rohloff, Catherine Manya, Berry, Stephen Andrew, Kang, Ling-Ling, Nathan, Aruna
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): DICKINSON, PAUL W
• Application Number:
  US13/100,016
• Publication Number:
  US 20110264076A1
• Time in Patent Office: 287 Days
• Field of Search: None
• US Class Current: 424/422
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• 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

Abstract

Liquid polyoxaester polymer materials are provided as suspending vehicles suitable for dispensing of pharmaceutically active agents, such as proteins, from delivery devices, for example, pump-driven dosage forms. Polyoxaesters are made from at least one diacid and at least one diol. Through the use of polyoxaesters virtually solvent-free pharmaceutical suspensions can be created.

Claims

1. An implantable osmotic dosage form comprising:

a pharmaceutical suspension comprising (i) particles comprising a protein or peptide, and (ii) a suspending vehicle comprising a polyoxaester having a density of about 1.2 g/mL, wherein the pharmaceutical suspension is substantially homogeneous for at least 3 months at 37°

C.;

a first wall that maintains its physical and chemical integrity and is substantially impermeable to a pharmaceutical suspension;

a second wall that is partially permeable to an exterior fluid;

an osmotic pump in contact with the first wall and the second wall;

a compartment defined by the first wall and the osmotic pump, wherein the pharmaceutical suspension is positioned within the compartment; and

an exit port in communication with the compartment, wherein the pharmaceutical suspension is flowable through the exit port under a force exerted by the osmotic pump.

2. A method of making the dosage form of claim 1 comprising, loading the pharmaceutical suspension into the compartment.

3. The dosage form of claim 1, wherein the pharmaceutical suspension is substantially free of solvents.

4. The dosage form of claim 1, wherein the polyoxaester comprises reaction products of at least one diacid and at least one diol.

5. The dosage form of claim 4, wherein the diacid is selected from the group consisting of a polyglycolic diacid;

a 3,6-trioxaundecanedioic diacid;

a 3,6,9-trioxaundecanedioic diacid; and

combinations thereof.

6. The dosage form of claim 4, wherein the diol is selected from the group consisting of an ethyleneglycol, a propanediol, a butanediol, a pentanediol, a cyclopentanediol, a hexanediol, a cyclohexanediol, an octanediol, a decanediol, a dodecanediol, a cyclohexanedimethanol, a polyethyleneglycol, a polypropyleneglycol, and combinations thereof.

7. The dosage form of claim 1, wherein the polyoxaester comprises condensation products of a mixture comprising a polyglycolic diacid and an ethyleneglycol.

8. The dosage form of claim 7, wherein the mixture further comprises a 3,6,9-trioxaundecanedioic diacid.

9. The dosage form of claim 7, wherein the polyoxaester has a molecular weight of from approximately 1,000 to approximately 100,000.

10. The dosage form of claim 1, wherein the polyoxaester comprises condensation products of a mixture comprising a 3,6,9-trioxaundecanedioic diacid and an ethyleneglycol.

11. The dosage form of claim 10, wherein the polyoxaester has a molecular weight of from approximately 1,000 to approximately 100,000.

12. The dosage form of claim 1, wherein the suspending vehicle consists essentially of the polyoxaester.

13. The dosage form of claim 1, wherein the osmotic pump comprises a piston and a fluid-imbibing agent.

14. The dosage form of claim 1, wherein the pharmaceutical suspension is substantially homogeneous for at least 6 months.

15. The dosage form of claim 1, wherein the pharmaceutical suspension is substantially homogeneous for at least 1 year.

16. The dosage form of claim 1, wherein the pharmaceutical suspension comprises from about 0.1% to about 30% of particles by weight.

17. The dosage form of claim 1, wherein the pharmaceutical suspension comprises from about 0.5% to about 15% of particles by weight.