Claims for Patent: 12,370,241

Summary for Patent: 12,370,241

Title:	Nasal powder formulation for treatment of hypoglycemia
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.
Inventor(s):	Sankaram Mantripragada, Claude A. Piche, Jo Jan Filip Van Betsbrugge
Assignee:	Amphastar Pharmaceuticals Inc
Application Number:	US18/167,260
Patent Claims:	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.