Methods of manufacturing viscous liquid pharmaceutical formulations

• US 9,724,293 B2
• Filed: 08/29/2012
• Issued: 08/08/2017
• Est. Priority Date: 11/17/2003
• Status: Expired due to Fees

• Current Assignee: Intarcia Therapeutics, Inc.
• Original Assignee: Intarcia Therapeutics, Inc.
• Inventors: Eliaz, Rom Ezer, Zhang, Yuanpeng, Rohloff, Catherine Manya, Weeks, Eric William, Junnarkar, Gunjan
• Primary Examiner(s): Park, Haejin Sarah
• Application Number:
  US13/598,405
• Publication Number:
  US 20130052237A1
• Time in Patent Office: 1,805 Days
• Field of Search: None
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 38/21 Interferons [IFN]
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• 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
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/06 of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH

Abstract

A liquid composition in an osmotic drug delivery system and a dosage form in an osmotic drug delivery system is disclosed comprising an amphiphilic molecule, a non-aqueous liquid solvent, and a pharmaceutically active agent.

Claims

1. A method of manufacturing a viscous, non-aqueous, liquid pharmaceutical formulation, comprising:

applying a shear rate to a viscous, non-aqueous, liquid-based suspending vehicle sufficient to produce a reduced viscosity liquid-based suspending vehicle;

mixing particles comprising a pharmaceutically active agent into the reduced viscosity liquid-based suspending vehicle at a temperature from 80°

C. to 120°

C., wherein the particles further comprise sucrose, methionine, and citrate buffer; and

processing the reduced viscosity liquid-based suspending vehicle to manufacture the viscous, non-aqueous, liquid pharmaceutical formulation,

wherein the viscous, non-aqueous, liquid-based suspending vehicle comprises;

an amphiphilic molecule; and

a solvent selected from the group consisting of;

lauryl lactate, lauryl alcohol, benzyl alcohol, benzyl benzoate, 1;

1 benzyl benzoate;

benzyl alcohol, ethyl hexyl lactate, glycerol formal, tetraglycol, N-1-methyl-2-pyrrolidone, dimethyl sulfoxide, polyethyleneglycol, triglycerides, ethanol, isopropanol, t-butyl alcohol, cyclohexanol, glycerin, glycerol, alpha-tocopherol, vegetable oil, sesame oil, soybean oil, cottonseed oil, and peanut oil wherein the pharmaceutically active agent is selected from the group consisting of a protein or a peptide.

2. The method of claim 1, further comprising maintaining the viscous, non-aqueous, liquid-based suspending vehicle at a target temperature while applying the shear rate.

3. The method of claim 2, further comprising maintaining the reduced viscosity liquid-based suspending vehicle at the target temperature while processing.

4. The method of claim 1, further comprising maintaining the reduced viscosity liquid-based suspending vehicle at a target temperature while processing.

5. The method of claim 1, further comprising:

maintaining the viscous, non-aqueous, liquid-based suspending vehicle at a first target temperature while applying the shear rate; and

maintaining the reduced viscosity liquid-based suspending vehicle at a second target temperature while processing.

6. The method of claim 1, wherein the amphiphilic molecule is selected from the group consisting of:

fatty acid esters, phospholipids, polyethyleneglycol-lipids, block copolymer surfactants, and sorbitan esters.

7. The method of claim 1, wherein the protein or the peptide is selected from the group consisting of omega-interferon, alpha-interferon, beta-interferon, gamma-interferon, erythropoietin, human growth hormone, granulocyte macrophage colony stimulating factor, human growth hormone releasing hormone, insulin, infliximab, glucagon-like peptide-1, and bone morphogenic protein.

8. The method of claim 1, wherein the particles comprise spray-dried particles.

9. The method of claim 8, wherein the particles comprise a diameter of about 1 μ

m to about 10 μ

m.

10. The method of claim 4, wherein the processing further comprises loading the reduced viscosity liquid-based suspending vehicle comprising the particles into a chamber of an osmotic drug delivery device.

11. The method of claim 1, wherein the viscous, non-aqueous, liquid-based suspending vehicle has a viscosity of about 5 poise to about 100,000 poise.

12. The method of claim 1, wherein the shear rate is about 0.04 per second to about 10 per second.

13. The method of claim 1, wherein the viscous, non-aqueous, liquid-based suspending vehicle comprises polyvinylpyrrolidone.