IP Library › Granted Patent US 12,508,229
Granted Patent B2
US 12,508,229 · App. 17/606,214 · Granted Dec 30, 2025

Method for preparing stable peptide formulations

Inventors: Gregory Nelson Brown (Indianapolis, IN); Kurt Gard Van Scoik (Carmel, IN)
Assignee: Amphastar Pharmaceuticals, Inc.
A61K9/19A61K9/0043A61K47/12A61K47/40A61K47/24
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Quick Facts
Patent No.
US 12,508,229
App. No.
17/606,214
Granted
Dec 30, 2025
Kind
B2
Abstract

The present invention provides an improved method for preparing a powder formulation containing a peptide. The present invention further provides an improved method for preparing a powder formulation containing glucagon or a glucagon analog, wherein said powder formulation is suitable for nasal administration.

Claims (28)

1 . A method for preparing a peptide powder formulation comprising the steps of:

a. forming a first mixture of an acid, a phospholipid surfactant, and a cyclodextrin in an aqueous carrier;

b. subjecting the first mixture to a first filtration step to generate a first filtration product wherein the filter comprises a membrane with a pore size of about 0.4 μm to about 0.5 μm;

c. adding a peptide to the first filtration product to form a second mixture, and subjecting the second mixture to a second filtration step to generate a second filtration product, wherein the filter comprises a membrane with a pore size of about 0.4 μm to about 0.5 μm; and

d. drying the second filtration product to form a solid formulation and processing the solid formulation to produce a final powder formulation, wherein the final powder formulation is suitable for nasal administration, wherein the second filtration product prior to drying is physically and chemically stable for twenty-four hours at 5° C. or for twenty-four hours at 20° C.

2 . The method of claim 1 wherein the peptide is glucagon or a glucagon analog.

3 . The method of claim 2 wherein the peptide is glucagon.

4 . The method of claim 1 wherein the surfactant, the cyclodextrin and the peptide together constitute between about 1.5% and about 3% by weight of the second mixture.

5 . The method of claim 4 wherein the surfactant, the cyclodextrin and the peptide together constitute about 2% by weight of the second mixture.

6 . The method of claim 4 wherein the surfactant, the cyclodextrin and the peptide together constitute about 2.5% by weight of the second mixture.

7 . The method of claim 1 wherein the membrane in both the first and the second filtration steps comprise a polyvinylidene difluoride (PVDF) membrane.

8 . The method of claim 1 wherein the membrane in both the first and the second filtration steps comprises a pore size of about 0.45 μm.

9 . The method of claim 1 wherein the acid is citric acid or acetic acid.

10 . The method of claim 9 wherein the acid is acetic acid.

11 . The method of claim 10 wherein the acetic acid is at a concentration of 1M.

12 . The method of claim 1 wherein the surfactant is dodecylphosphocholine, didecylphosphatidylcholine, lysolauroylphosphatidylcholine, dioctanoylphosphatidylcholine, or dilauroylphosphatidylglycerol.

13 . The method of claim 12 wherein the surfactant is dodecylphosphocholine.

14 . The method of claim 1 wherein the cyclodextrin is α-cyclodextrin, β-cyclodextrin, hydroxypropyl β-cyclodextrin, or γ-cyclodextrin.

15 . The method of claim 14 wherein the cyclodextrin is β-cyclodextrin.

16 . The method of claim 1 , wherein the processing the solid formulation comprises densification.

17 . The method of claim 1 , wherein the peptide is glucagon, the acid is acetic acid, the phospholipid surfactant is dodecylphosphocholine, and the cyclodextrin is β-cyclodextrin.

18 . The method of claim 17 wherein the dodecylphosphocholine, the β-cyclodextrin and the glucagon together constitute about 2.5% by weight of the second mixture.

19 . The method of claim 17 wherein the membrane in both the first and the second filtration steps comprises a PVDF membrane.

20 . The method of claim 17 wherein the membrane in both the first and the second filtration steps comprises a pore size of about 0.45 μm.

21 . The method of claim 17 wherein the acetic acid is at a concentration of 1M.

22 . The method of claim 17 wherein greater than 98% of the glucagon in the final powder formulation is non-aggregated glucagon as measured by reversed phase-HPLC.

23 . The method of claim 17 , wherein the final powder formulation comprises glucagon, dodecylphosphocholine, and β-cyclodextrin in a weight ratio of 10:10:80 (glucagon:dodecylphosphocholine:β-cyclodextrin).

24 . The method of claim 17 , wherein the processing the solid formulation comprises densification.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 10, 2023
From: ELI LILLY AND COMPANY
To: AMPHASTAR PHARMACEUTICALS, INC.
Reel/Frame 064553/0910 →
SECURITY INTEREST Recorded Jun 30, 2023
From: AMPHASTAR PHARMACEUTICALS, INC.
To: WELLS FARGO BANK, NATIONAL ASSOCIATION, AS ADMINISTRATIVE AGENT
Reel/Frame 064124/0933 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 25, 2021
From: BROWN, GREGORY NELSON; VAN SCOIK, KURT GARD
To: ELI LILLY AND COMPANY
Reel/Frame 057900/0185 →
Continuity (2)
Provisional Application 62839246 · Apr 26, 2019
Related Publication 20220192988A1 · Jun 23, 2022
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