IP Library › Granted Patent US 12,370,241
Granted Patent B2
US 12,370,241 · App. 18/167,260 · Granted Jul 29, 2025

Nasal powder formulation for treatment of hypoglycemia

Inventors: Sankaram Mantripragada (Windsor, CO); Claude A. Piche (Verdun, CA); Jo Jan Filip Van Betsbrugge (Laval, CA)
Assignee: Amphastar Pharmaceuticals, Inc.
A61K38/26A61K9/0043A61K9/145A61K9/146A61K31/724A61K47/12A61K47/24A61M15/0065A61M15/08A61M2202/064
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Quick Facts
Patent No.
US 12,370,241
App. No.
18/167,260
Granted
Jul 29, 2025
Kind
B2
Abstract

The present invention provides a powder formulation containing glucagon or a glucagon analog for nasal administration, useful in the treatment of hypoglycemia, and in particular the treatment of severe hypoglycemia. The present invention also provides a method of making this powder formulation, and to devices and methods for using the powder formulation.

Claims (24)

1. A powder composition comprising glucagon (SEQ ID NO:1), a phospholipid surfactant and a cyclodextrin selected from the group consisting of α-cyclodextrin, β-cyclodextrin, hydroxypropyl-β-cyclodextrin, or γ-cyclodextrin, wherein the ratio of glucagon to phospholipid surfactant to cyclodextrin is 1:1:8 by weight, wherein at least a portion of the powder composition is present in a phase characterized by an XRPD mesopeak as determined by x-ray powder diffraction, and wherein said powder composition is prepared according to a method comprising the steps of:

a. forming a first mixture of the glucagon (SEQ ID NO. 1) and the phospholipid surfactant in an aqueous carrier, wherein the phospholipid surfactant is present in a concentration greater than or equal to the critical micelle concentration;

b. adding the cyclodextrin to the first mixture to form a second mixture;

c. drying the second mixture to form a solid formulation; and

d. processing the solid formulation to produce a uniform powder, said uniform powder including at least a portion of the powder in a phase characterized by an XRPD mesopeak.

2. The powder composition according to claim 1 , wherein the phospholipid surfactant is selected from the group consisting of dodecylphosphocholine, didecylphosphatidylcholine, lysolauroylphosphatidylcholine, dioctanoylphosphatidylcholine and dilauroylphosphatidylglycerol.

3. The powder composition according to claim 1 , wherein the cyclodextrin is an α-cyclodextrin or a β-cyclodextrin.

4. The powder composition according to claim 1 , further comprising up to 10 wt % of the overall weight of the composition of sodium citrate or citric acid.

5. The powder composition according to claim 1 , wherein the drying of the second mixture is carried out by freeze drying or spray drying the second mixture.

6. A nasal applicator for a powder composition, said applicator comprising a powder formulation reservoir, and further comprising the powder composition of claim 1 contained within the reservoir.

7. A method for treating hypoglycemia in an individual suffering from hypoglycemia comprising administering to the individual the powder composition of claim 1 , wherein the composition is administered in a therapeutically effective amount as a powder to the nasal mucosa of the individual.

8. A powder composition comprising glucagon (SEQ ID NO:1), a phospholipid surfactant and a cyclodextrin selected from the group consisting of α-cyclodextrin, β-cyclodextrin, hydroxypropyl-β-cyclodextrin, or γ-cyclodextrin, wherein the ratio of glucagon to phospholipid surfactant to cyclodextrin is 1:1:8 by weight, and wherein said powder composition is prepared according to a method comprising the steps of:

a. forming a first mixture of the glucagon (SEQ ID NO. 1) and the phospholipid surfactant in an aqueous carrier, wherein the phospholipid surfactant is present in a concentration greater than or equal to the critical micelle concentration;

b. adding the cyclodextrin to the first mixture to form a second mixture;

c. drying the second mixture to form a solid formulation; and

d. processing the solid formulation to produce a uniform powder.

9. The powder composition according to claim 8 , wherein the phospholipid surfactant is selected from the group consisting of dodecylphosphocholine, didecylphosphatidylcholine, lysolauroylphosphatidylcholine, dioctanoylphosphatidylcholine and dilauroylphosphatidylglycerol.

10. The powder composition according to claim 8 , wherein the cyclodextrin is an α-cyclodextrin or a β-cyclodextrin.

11. The powder composition according to claim 8 , further comprising up to 10 wt % of the overall weight of the composition of sodium citrate or citric acid.

12. The powder composition according to claim 8 wherein the drying of the second mixture is carried out by freeze drying or spray drying the second mixture.

13. A nasal applicator for a powder composition, said applicator comprising a powder formulation reservoir, and further comprising the powder composition of claim 8 contained within the reservoir.

14. A method for treating hypoglycemia in an individual suffering from hypoglycemia comprising administering to the individual the powder composition of claim 8 , wherein the composition is administered in a therapeutically effective amount as a powder to the nasal mucosa of the individual.

15. The powder composition of claim 1 , wherein the powder composition comprises glucagon (SEQ ID NO: 1), a phospholipid, and β-cyclodextrin in a ratio of glucagon to phospholipid to β-cyclodextrin of 1:1:8 by weight.

16. The powder composition of claim 8 , wherein the powder composition comprises glucagon (SEQ ID NO: 1), a phospholipid, and β-cyclodextrin in a ratio of glucagon to phospholipid to β-cyclodextrin of 1:1:8 by weight.

Assignments (2)
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 →
Continuity (4)
Continuation 16266640 · Feb 4, 2019
Continuation 15545332
Provisional Application 62117031 · Feb 17, 2015
Related Publication 20230302093A1 · Sep 28, 2023
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