Stable non-aqueous single phase viscous vehicles and formulations utilizing such vehicle

• US 7,258,869 B1
• Filed: 02/03/2000
• Issued: 08/21/2007
• Est. Priority Date: 02/08/1999
• Status: Expired due to Fees

• Current Assignee: Intarcia Therapeutics, Inc.
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Dehnad, Houdin, Berry, Stephen A., Fereira, Pamela J., Muchnik, Anna
• Primary Examiner(s): Hartley; Michael G.
• Assistant Examiner(s): FUBARA, BLESSING M
• Application Number:
  US09/497,422
• Time in Patent Office: 2,756 Days
• Field of Search: 424/422, 424/449, 424/423, 514/937
• US Class Current: 424/422
• CPC Class Codes: A61K 38/27 Growth hormone [GH], i.e. somatotropin
• 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 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• 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 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 47/44 Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14
• 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
• CPC Class Codes: A61M 2205/04 implanted
• CPC Class Codes: A61M 5/14224 Diaphragm type
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61M 5/145 using pressurised reservoirs, e.g. pressurised by means of pistons
• CPC Class Codes: Y10T 29/49826 Assembling or joining

Abstract

This invention relates to stable non-aqueous single phase viscous vehicles and to formulations utilizing such vehicles. The formulations comprise at least one beneficial agent uniformly suspended in the vehicle. The formulation is capable of being stored at temperatures ranging from cold to body temperature for long periods of time. The formulations are capable of being uniformly delivered from drug delivery systems at an exit shear rate of between about 1 to 1×10⁻⁷ reciprocal second.

Claims

1. A stable non-aqueous single-phase biocompatible viscous vehicle, comprising:

a polymer consisting of polyvinylpyrrolidone;

a surfactant consisting of glycerol monolaurate; and

a solvent consisting of laurel lacate;

wherein the viscosity of the vehicle is between about 1,000 and about 10,000,000 poises.

2. A stable non-aqueous single-phase biocompatible viscous vehicle comprising:

a polymer consisting of polyvinylpyrrolidone;

a surfactant consisting of polysorbate; and

a solvent consisting of lauryl lactate;

wherein the viscosity of the vehicle is between about 1,000 and about 10,000,000 poise.

3. A non-aqueous formulation comprising at least one beneficial agent uniformly suspended in a non-aqueous single-phase biocompatible viscous vehicle, the non-aqueous single-phase biocompatible viscous vehicle comprising:

a polymer consisting of glycerol monolaurate or polysorbate; and

a solvent consisting of lauryl lactate.

4. A stable non-aqueous viscous protein formulation that is capable of being uniformly dispensed over an extended period of time at a low flow rate and is stable at body temperature for extended periods of time, the stable non-aqueous viscous protein formulation comprising:

a) at least one protein; and

b) a non-aqueous single-phase biocompatible viscous vehicle comprising a polymer consisting of polyvinylpyrrolidone, a surfactant consisting of glycerol monolaurate or polysorbate, and a solvent consisting of lauryl lactate.

5. The stable non-aqueous viscous protein formulation of claim 4, wherein the at least one protein is present in an amount of at least about 0.1% (w/w).

6. The stable non-aqueous viscous protein formulation of claim 4, wherein the at least one protein is present in an amount of at least about 10% (w/w).

7. The formulation of claim 4, wherein the stable non-aqueous viscous protein formulation is capable of being uniformly dispensed over an extended period of time at a low flow rate and is stable at 65°

C. for at least about 2 months.

8. The formulation of claim 4, wherein the stable non-aqueous viscous protein formulation is capable of being uniformly dispensed over an extended period of time at a low flow rate and is stable at 37°

C. for at least about 3 months.

9. The formulation of claim 4, wherein the viscosity of the vehicle is between about 1,000 and about 10,000,000 poise.

10. The formulation of claim 4, wherein the beneficial agent is dried to a low moisture content prior to incorporated in the stable non-aqueous viscous protein formulation.

11. A method for preparing a stable non-aqueous single-phase biocompatible viscous vehicle, the method comprising:

(1) selecting a polymer consisting of polyvinylpyrrolidone, a surfactant consisting of glycerol monolaurate or polydsorbate, and a solvent consisting of lauryl lactate;

(2) blending the polymer, the surfactant, and the solvent at elevated temperature under dry conditions to allow the polymer, the surfactant, and the solvent to liquefy; and

(3) allowing the liquefied components to cool to room temperature such that a stable non-aqueous single-phase biocompatible viscous vehicle is formed.

12. The method of claim 11, wherein the viscosity of the vehicle is between about 1,000 and about 10,000,000 poise.

13. The method of claim 11, wherein the at least one beneficial agent is present in an amount of at least about 0.1%°

(w/w).

14. The method of claim 11, wherein the at least one beneficial agent is present in an amount of at least about 10%°

(w/w).