Claims for Patent: 11,173,189

Summary for Patent: 11,173,189

Title:	Daptomycin formulations containing a combination of sorbitol and mannitol
Abstract:	In an aspect, a method of manufacture of a pharmaceutically acceptable solid composition containing daptomycin includes drying an aqueous solution containing (i) water, (ii) the daptomycin, (iii) sorbitol in an amount of about 1.2 wt. % to about 9.0 wt. % of total volume of the aqueous composition and (iv) mannitol in an amount of about 0.6 wt. % to about 9.5 wt. % of total volume of the aqueous composition to form the solid composition. The drying can include an sublimation drying of about -25.degree. C. to about 50.degree. C. for a time period of about 15 hours to about 120 hours, most preferably about 15.degree. C. for about 20 hours, optionally preceded and/or followed by one or more additional drying steps. Other aspects are the solid composition containing the daptomycin and also methods of treating a bacterial infection including administering a pharmaceutically acceptable product made by reconstituting the solid composition.
Inventor(s):	Wegiel; Lindsay (Martinsville, IN), Miller; Reagan (Grayslake, IL)
Assignee:	Baxter International Inc. (Deerfield, IL) Baxter Healthcare SA (Glattpark, CH)
Application Number:	17/199,086
Patent Claims:	1. A method of making a pharmaceutically acceptable solid composition comprising daptomycin, the method comprising drying an aqueous solution to form the solid composition with a moisture content of about 1.0 wt. % or less relative to total weight of the solid composition, the aqueous solution comprising (a) water, (b) the daptomycin, (c) sorbitol in an amount of about 1.2 wt. % to about 9.0 wt. % of total volume of the aqueous solution and (d) mannitol in an amount of about 0.6 wt. % to about 9.5 wt. % of the total volume of the aqueous solution, and the aqueous solution contains less than about 0.5 wt. % buffering agent. 2. The method of claim 1, wherein the sorbitol is about 4.0 wt. % to about 5.0 wt. % of the total volume of the aqueous solution, and the mannitol is about 4.0 wt. % to 5.0 wt. % of the total volume of the aqueous solution. 3. The method of claim 1, wherein the aqueous solution has a daptomycin:(sorbitol+mannitol) molar ratio from about 1:4 to about 1:13 and a sorbitol:mannitol weight ratio from 20:80 to 40:60. 4. The method of claim 1, wherein the aqueous solution has a daptomycin:(sorbitol+mannitol) molar ratio from about 1:5 to about 1:13 and a sorbitol:mannitol weight ratio of about 30:70. 5. The method of claim 1, wherein the aqueous solution has a daptomycin:(sorbitol+mannitol) molar ratio from about 1:4 to about 1:9 and a sorbitol:mannitol weight ratio above 40:60 up to 90:10. 6. The method of claim 1, wherein the aqueous solution has a daptomycin:(sorbitol+mannitol) molar ratio from about 1:4 to about 1:8.5 and a sorbitol:mannitol weight ratio about 50:50 to about 70:30. 7. The method of claim 1, comprising adjusting the pH of the aqueous solution to about 4.5 to about 8.0 before the drying of the aqueous solution. 8. The method of claim 1, comprising adjusting the pH of the aqueous solution to about 7.0 before the drying of the aqueous solution. 9. The method of claim 1, wherein the aqueous solution contains substantially no sugars and/or contains substantially no other polyols additional to the sorbitol and the mannitol. 10. The method of claim 1, wherein the aqueous solution contains less than about 0.1 wt. % buffering agent. 11. The method of claim 1, wherein the aqueous solution consists essentially of the daptomycin, the sorbitol, the mannitol, and the water. 12. The method of claim 1, wherein the pharmaceutically acceptable solid composition has an increase in Impurity D7, after storage at 25.degree. C. for 6 months after the drying of the aqueous solution, that is no greater than about 1.00% relative to an initial amount of the Impurity D7 in the pharmaceutically acceptable solid composition at the beginning of the storage, as measured by peak area of the Impurity D7 divided by peak area of the daptomycin and total impurities using Ultra Performance Liquid Chromatography. 13. The method of claim 1, wherein the drying comprises a sublimation drying at a temperature of about -25.degree. C. to about 50.degree. C. for a time period of about 15 hours to about 120 hours. 14. The method of claim 13, wherein the temperature of the sublimation drying is about 10.degree. C. to about 20.degree. C., and the time period of the sublimation drying is about 18 hours to about 25 hours. 15. The method of claim 13, wherein the drying is a process selected from the group consisting of (i) the process comprises the sublimation drying, (ii) the process comprises the sublimation drying and one or more preceding drying steps, (iii) the process comprises the sublimation drying and one or more subsequent drying steps and (iv) the process comprises the sublimation drying, one or more preceding drying steps, and one or more subsequent drying steps. 16. A pharmaceutically acceptable solid composition made by the method of claim 1. 17. A pharmaceutically acceptable solid composition comprising daptomycin and a combination of sorbitol and mannitol and having a moisture content of about 1.0 wt. % or less, wherein the sorbitol is about 6.2 wt. % to about 45.3 wt. % of total weight of the pharmaceutically acceptable solid composition, the mannitol is about 3.1 wt. % to about 47.5 wt. % of the total weight of the pharmaceutically acceptable solid composition, and the total of the sorbitol and the mannitol is about 31.0 wt. % to about 59.4 wt. % of the total weight of the pharmaceutically acceptable solid composition. 18. The pharmaceutically acceptable solid composition of claim 17, having a daptomycin:(sorbitol+mannitol) molar ratio from about 1:4 to about 1:13 and a sorbitol:mannitol weight ratio from 20:80 to 40:60. 19. The pharmaceutically acceptable solid composition of claim 18, wherein the daptomycin:(sorbitol+mannitol) molar ratio is from about 1:5 to about 1:13, and the sorbitol:mannitol weight ratio is about 30:70. 20. The pharmaceutically acceptable solid composition of claim 18, wherein the sorbitol is about 6.2 wt. % to about 22.1 wt. % of the total weight of the pharmaceutically acceptable solid composition, the mannitol is about 18.6 wt. % to about 47.5 wt. % of the total weight of the pharmaceutically acceptable solid composition, and the total of the sorbitol and the mannitol is about 31.0 wt. % to about 59.4 wt. % of the total weight of the solid composition. 21. The pharmaceutically acceptable solid composition of claim 18, wherein the aqueous solution has a daptomycin:(sorbitol+mannitol) molar ratio from about 1:4 to about 1:9 and a sorbitol:mannitol weight ratio above 40:60 up to 90:10. 22. The pharmaceutically acceptable solid composition of claim 21, wherein the daptomycin:(sorbitol+mannitol) molar ratio is from about 1:4 to about 1:8.5, and the sorbitol:mannitol weight ratio is about 50:50 to about 70:30. 23. The pharmaceutically acceptable solid composition of claim 21, wherein the sorbitol is about 15.5 wt. % to about 45.3 wt. % of the total weight of the pharmaceutically acceptable solid composition, the mannitol is about 3.1 wt. % to about 25.2 wt. % of the total weight of the pharmaceutically acceptable solid composition, and the total of the sorbitol and the mannitol is about 31.0 wt. % to about 50.3 wt. % of the total weight of the pharmaceutically acceptable solid composition. 24. The pharmaceutically acceptable solid composition of claim 17, having an increase in Impurity D7, after storage at 25.degree. C. for 6 months after the drying of the aqueous solution, that is no greater than about 1.00% relative to an initial amount of the Impurity D7 in the pharmaceutically acceptable solid composition at the beginning of the storage, as measured by peak area of the Impurity D7 divided by peak area of the daptomycin and total impurities using Ultra Performance Liquid Chromatography. 25. The pharmaceutically acceptable solid composition of claim 17, which contains substantially no sugars and/or contains substantially no other polyols additional to the sorbitol and the mannitol. 26. The pharmaceutically acceptable solid composition of claim 17, which contains substantially no buffering agent. 27. The pharmaceutically acceptable solid composition of claim 17, which consists essentially of the daptomycin, the sorbitol, the mannitol, and the moisture content of about 1.0 wt. % or less. 28. The pharmaceutically acceptable solid composition of claim 17, further comprising sodium hydroxide and hydrogen chloride. 29. A method of treating a bacterial infection in a subject having the bacterial infection, the method comprising: preparing a pharmaceutical product, wherein the preparing of the pharmaceutical product comprises reconstituting, in a pharmaceutically acceptable diluent, the pharmaceutically acceptable solid composition of claim 17; and administering an effective amount of the pharmaceutical product to the subject. 30. The method of claim 29, wherein the administering comprises intravenous administration.