Claims for Patent: 12,629,337

Summary for Patent: 12,629,337

Title:	Daptomycin formulation
Abstract:	The present disclosure relates to a solid formulation of daptomycin comprising at least one branched aliphatic amino acid. Solid daptomycin formulation of the present disclosure shows improved reconstituted time. The disclosure further relates to a method of preparation of the solid daptomycin formulation according to this disclosure.
Inventor(s):	Barbara FUMIC
Assignee:	Hikma Pharmaceuticals USA Inc
Application Number:	US17/794,734
Patent Claims:	1. A solid pharmaceutically acceptable formulation of daptomycin, wherein said formulation is prepared by lyophilizing an aqueous daptomycin solution comprising daptomycin and at least one branched chain aliphatic amino acid or a pharmaceutically acceptable salt thereof, wherein the aliphatic side chain of the at least one branched chain aliphatic amino acid comprises a branch, and wherein a reconstitution time of 500 mg of the solid pharmaceutical daptomycin formulation in 10 mL of 0.9% sodium chloride at controlled room temperature is less than 120 seconds, wherein the solid formulation does not include an amino sugar. 2. The solid formulation of daptomycin according to claim 1, wherein the at least one branched chain aliphatic amino acid comprises Leucine, Isoleucine, or Valine. 3. The solid formulation of daptomycin according to claim 2, wherein the at least one branched chain aliphatic amino acid is selected from L-Leucine, L-Isoleucine, and L-Valine. 4. The solid formulation of daptomycin according to claim 3, wherein the at least one branched chain aliphatic amino acid is L-Isoleucine. 5. The solid formulation of daptomycin according to claim 3, wherein the at least one branched chain aliphatic amino acid is L-Valine. 6. The solid formulation of daptomycin according to claim 1, wherein the branched chain aliphatic amino acid, prior to lyophilizing, is present in an amount of 2.5% w/V or less. 7. The solid formulation of daptomycin according to claim 1, wherein the branched chain aliphatic amino acid, prior to lyophilizing, is present in an amount of 1% w/V or less. 8. The solid formulation of daptomycin according to claim 4, wherein the formulation prior to lyophilizing comprises 10% w/V of daptomycin and 0.8% w/V of L-Isoleucine. 9. The solid formulation of daptomycin according to claim 1, wherein a pH of the formulation prior to lyophilizing is from 4.5 to 9. 10. The solid formulation of daptomycin according claim 1, wherein a pH of the formulation prior to lyophilizing is from 6 to 6.5. 11. The solid formulation of daptomycin according to claim 1, wherein the at least one branched chain aliphatic amino acid is present in a molar ratio to daptomycin from 0.5:1 to 5:1. 12. The solid formulation of daptomycin according to claim 1, wherein the at least one branched chain aliphatic amino acid is present in a molar ratio to daptomycin from 1:1 to 3:1. 13. The solid formulation of daptomycin according to claim 4, having an improved reconstitution time from 60% to 96% compared to the reconstitution time of a solid daptomycin formulation which does not contain at least one branched chain aliphatic amino acid. 14. The solid formulation of daptomycin according to claim 4, having an improved reconstitution time from 80% to 96% compared to the reconstitution time of a solid daptomycin formulation which is stored in refrigerated conditions and has as an inactive ingredient only sodium hydroxide for pH adjustment. 15. The solid formulation of daptomycin according to claim 1, comprising at least one excipient for stabilization. 16. The solid formulation of daptomycin according to claim 15, wherein the at least one excipient for stabilization comprises Alanine, Arginine, Asparagine, Histidine, Glycine, Lysine, Ornithine, Phenylalanine, Proline, Threonine, Tryptophan, Tyrosine, or a pharmaceutically acceptable salt thereof. 17. The solid formulation of daptomycin according to claim 16, wherein the at least one excipient for stabilization is selected from Arginine, Histidine, or a pharmaceutically acceptable salt thereof. 18. The solid formulation of daptomycin according to claim 16, wherein the formulation comprises two excipients for stabilization, wherein a first excipient for stabilization is Arginine, or a pharmaceutically acceptable salt thereof, and a second excipient for stabilization is Histidine, or a pharmaceutically acceptable salt thereof. 19. The solid formulation of daptomycin according to claim 16, wherein the excipient for stabilization is present in a molar ratio to daptomycin from 3:1 to 5:1. 20. The solid formulation of daptomycin according to claim 16, wherein the solid formulation of daptomycin comprises Isoleucine, or a pharmaceutically acceptable salt thereof as the branched chain aliphatic amino acid, and at least one excipient for stabilization selected from Arginine, Histidine, or a pharmaceutically acceptable salt thereof. 21. The solid formulation of daptomycin according to claim 19, wherein the solid formulation of daptomycin comprises Isoleucine, or a pharmaceutically acceptable salt thereof as the branched chain aliphatic amino acid, and two excipients for stabilization that are Arginine, Histidine, or a pharmaceutically acceptable salt thereof, wherein a molar ratio of daptomycin to the excipients Dapt:Ile:Arg:His is from 1:0.5:1:1 to 1:3:5:5. 22. The solid formulation of daptomycin according to claim 19, wherein the solid formulation of daptomycin comprises Isoleucine, or a pharmaceutically acceptable salt thereof as the branched chain aliphatic amino acid, and two excipients for stabilization that are Arginine, Histidine, a pharmaceutically acceptable salt thereof, wherein a molar ratio of daptomycin to the excipients Dapt:Ile:Arg:His is 1:1:5:3. 23. The solid formulation of daptomycin according to claim 16, wherein the solid formulation of daptomycin comprises L-Isoleucine as the branched chain aliphatic amino acid, and an excipient for stabilization selected from Arginine and Histidine, wherein a molar ratio of daptomycin to said excipients Dapt:Ile:Arg:His is 1:1:5:3, and wherein a reconstitution time of 500 mg of solid formulation of daptomycin in 10 mL of water for injection at controlled room temperature is 50 seconds or less. 24. The solid formulation of daptomycin according to claim 16, wherein the solid formulation of daptomycin comprises L-Isoleucine as the branched chain aliphatic amino acid and an excipient for stabilization selected from Arginine and Histidine, wherein a molar ratio of daptomycin to said excipients Dapt:Ile:Arg:His is 1:1:5:3, wherein the formulation has an improved reconstitution time, wherein improved reconstitution time is a reduction of reconstitution time of 75% or more compared to a reconstitution time of a solid daptomycin formulation comprising excipients for stabilization selected from Arginine and Histidine, wherein a molar ratio of daptomycin to said excipients Dapt:Arg:His is 1:5:3. 25. A method of producing a solid formulation of daptomycin according to claim 1, wherein the method comprises providing a solution of the daptomycin and the at least one branched chain aliphatic amino acid, adjusting the pH of the solution to pH from 4 to 9 with a pH adjusting agent, and lyophilizing the solution. 26. A method of improving a reconstitution time of a solid formulation of daptomycin comprising providing at least one branched chain aliphatic amino acid in preparing the solid formulation of daptomycin. 27. The solid formulation of daptomycin according to claim 1, wherein the solid formulation does not include a surfactant, a sugar alcohol, an organic solvent, a divalent cation, a cyclodextrin, or a combination thereof.