Peptide/protein suspending formulations

• US 5,904,935 A
• Filed: 06/07/1995
• Issued: 05/18/1999
• Est. Priority Date: 06/07/1995
• Status: Expired due to Term

• Current Assignee: Intarcia Therapeutics, Inc.
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Wright, Jeremy, Leonard, John Joseph Jr., Leung, Iris K. M., Magruder, Judy A., Holladay, Leslie A., Carr, John P., Tao, Sally A., Eckenhoff, deceased, James B.
• Primary Examiner(s): Ketter, James
• Assistant Examiner(s): SANDALS, WILLIAM O
• Application Number:
  US08/475,238
• Time in Patent Office: 1,441 Days
• Field of Search: 424/198.1, 424/489, 424/499, 424/502, 514/2, 514/44, 530/35, 530/351
• US Class Current: 424/489
• 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 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas

Abstract

The present invention provides improved compositions for improving the chemical and physical stability of peptides and proteins. The invention provides a liquid beneficial agent formulation containing a liquid suspension comprising at least 5% by weight beneficial agent and having a viscosity and beneficial agent size which minimizes settling of the agent in suspension over the extended delivery period.

Claims

1. A beneficial agent formulation for use in a device which delivers the formulation over an extended delivery period, the formulation comprising:

(a) at least 5% by weight beneficial agent in the form of solid particles, the beneficial agent particle size being 0.3 to 50 microns; and

(b) a liquid suspension vehicle for suspending the particles in the formulation, wherein the liquid suspension formulation viscosity is sufficient to prevent settling of the agent in the liquid suspension formulation in the device over the extended delivery period.

2. The formulation of claim 1, wherein the particle size is between 1 to 10 microns.

3. The formulation of claim 1, wherein the viscosity is 100 to 100,000 poise at 37°

C.

4. The formulation of claim 1, wherein the extended delivery period is at least about 1 month.

5. The formulation of claim 1, wherein the beneficial agent is a water sensitive compound.

6. The formulation of to claim 1, wherein the suspension vehicle comprises a low molecular weight polyol and a thickening agent.

7. The formulation of claim 5 wherein the polyol is polyethylene glycol having a molecular weight between 200 and 1000.

8. The formulation of claim 7 wherein the thickening agent comprises povidone.

9. The formulation of claim 6 wherein the polyol is polyethylene glycol having a molecular weight between 200 and 600.

10. The formulation of claim 9 wherein the thickening agent comprises povidone or hydroxypropyl cellulose.

11. The formulation of claim 1, wherein the beneficial agent is human α

-interferon.

12. The formulation of claim 11, wherein the concentration of interferon is at least 1×

10⁹ IU.

13. A formulation for sustained controlled delivery from a delivery device over an extended delivery period, the formulation comprising:

(a) 0.5 to 70% by weight beneficial agent in the form of solid particles having a particle size of 0.3 to 50 microns; and

(b) a non-aqueous liquid suspension vehicle comprising a non-aqueous vehicle for suspending the particles in the formulation, polyethylene glycol with a molecular weight of 200 to 1000, and a thickening agent, which is characterized by a formulation viscosity of 100 to 100,000 poise at 37°

C. wherein said formulation viscosity is sufficient to prevent settling of the agent in the suspension formulation in the delivery device over the period of extended delivery.

14. A formulation according to claim 13 wherein the thickening agent is selected from the group consisting of povidone and hydroxypropyl cellulose.