Method of manufacturing an osmotic delivery device

• US 10,363,287 B2
• Filed: 06/02/2017
• Issued: 07/30/2019
• Est. Priority Date: 02/03/2005
• Status: Active Grant

• Current Assignee: Intarcia Therapeutics, Inc.
• Original Assignee: Intarcia Therapeutics, Inc.
• Inventors: Alessi, Thomas R., Mercer, Ryan D., Rohloff, Catherine M., Yang, Bing
• Primary Examiner(s): Chandra, Gyan
• Application Number:
  US15/612,581
• Publication Number:
  US 20170368145A1
• Time in Patent Office: 788 Days
• CPC Class Codes: A61K 38/26 Glucagons
• 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 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• 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 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: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• 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: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/48 of the pancreatic hormones
• CPC Class Codes: A61P 5/50 for increasing or potentiating the activity of insulin
• CPC Class Codes: C07K 14/605 Glucagons
• CPC Class Codes: C07K 7/067 Hemoregulatory peptides based on sequence Glp-Glu-Asp-Cys-Lys
• CPC Class Codes: Y10T 29/494 Fluidic or fluid actuated device making

Abstract

A suspension formulation of an insulinotropic peptide (e.g., glucagon-like peptide-1 (GLP-1) or exenatide) is described. The suspension formulation comprises (i) a non-aqueous, single-phase vehicle, comprising one or more polymer and one or more one solvent, wherein the vehicle exhibits viscous fluid characteristics, and (ii) a particle formulation comprising the insulinotropic peptide, wherein the peptide is dispersed in the vehicle. The particle formulation further includes a stabilizing component comprising one or more stabilizers, for example, carbohydrates, antioxidants, amino acids, and buffers. Devices for delivering the suspension formulations and methods of use are also described.

Claims

1. A method of manufacturing an osmotic delivery device comprising loading a suspension formulation into a reservoir of the osmotic delivery device,

the suspension formulation comprising:

a particle formulation comprising

an insulinotropic peptide, an antioxidant, and a buffer, wherein the insulinotropic peptide is at least one of exenatide, a derivative of exenatide, and an analogue of exenatide; and

a non-aqueous, single-phase suspension vehicle that comprises about 20 wt % to about 60 wt % solvent and about 80 wt % to about 40 wt % pyrrolidone polymer, the suspension vehicle having a viscosity from 5,000 poise to 50,000 poise at 33°

C.;

wherein;

the solvent is at least one of lauryl lactate, lauryl alcohol, and benzyl benzoate;

30 to 90% by weight of the particle formulation is the insulinotropic peptide;

the particle formulation has a wt % ratio of insulinotropic peptide to antioxidant of 2.5/1 to 10/1; and

the particle formulation is dispersed in the suspension vehicle.

2. The method of claim 1, wherein the insulinotropic peptide is exenatide.

3. The method of claim 1, wherein the buffer is selected from at least one of citrate, histidine, succinate, and tris.

4. The method of claim 3, wherein the buffer is citrate.

5. The method of claim 1, wherein the antioxidant is methionine.

6. The method of claim 1, wherein the solvent is benzyl benzoate.

7. The method of claim 1, wherein the pyrrolidone polymer is polyvinylpyrrolidone.

8. The method of claim 1, wherein the particle formulation further comprises a carbohydrate.

9. The method of claim 7, wherein the carbohydrate is at least one of lactose, sucrose, trehalose, cellobiose, and raffinose.

10. The method of claim 9, wherein the carbohydrate is sucrose.

11. The method of claim 8, wherein the particle formulation comprises exenatide, sucrose, methionine, and citrate.

12. The method of claim 11, wherein the particle formulation has a wt % ratio of insulinotropic peptide to antioxidant of 5/1 to 10/1.

13. The method of claim 12, wherein the solvent is benzyl benzoate.

14. The method of claim 13, wherein the pyrrolidone polymer is polylvinylpyrrolidone.

15. The method of claim 14, wherein the particle formulation has a moisture content of less than 5 wt %.

16. The method of claim 15, wherein particles of the particle formulation have a diameter of about 3 μ

m to about 50 μ

m.