Granted Patent B2

US 9,724,293 · App. 13/598,405 · Granted Aug 8, 2017

Abstract

Claims (21)

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 μm to about 10 μm.

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.

Assignments (8)