Claims for Patent: 12,390,442

Summary for Patent: 12,390,442

Title:	Artesunate powders, pharmaceutical compositions and methods of manufacture
Abstract:	Disclosed herein are powders including a therapeutically effective amount of 4-oxo-4-[[(1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]1exadecane-10-yl]oxy]butanoic acid (artesunate) or a pharmaceutically acceptable salt thereof that can be easily manufactured, sterilized and packaged. Processes for producing these powders and pharmaceutical compositions containing these powders are also disclosed.
Inventor(s):	Bryan L. Smith, Lisa Thomas Read
Assignee:	Amivas Inc
Application Number:	US18/908,438
Patent Claims:	1. A method of treating a malaria in a subject in need thereof, the method comprising obtaining a micronized powder comprising a therapeutically effective amount of 4-oxo-4-[[(1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]oxy]butanoic acid (artesunate) or a pharmaceutically acceptable salt thereof, wherein the micronized powder contains: (i) a crystalline form of artesunate or the pharmaceutically acceptable salt thereof in a concentration above 0 wt % to about 1 wt % of the total weight of the powder, and (ii) has an average static charge from about −0.05 kV to 0.05 kV according to a static charge test that includes: (i) subjecting the powder to a relative humidity of about 30% to 40% for at least five days, (ii) placing the powder onto a piece of weighing paper, (iii) measuring the static charge of the powder with a static meter at least three times, wherein the measuring of the static charge of the powder with a static meter occurs at least 25 millimeters from the surface of the powder, and (iv) calculating the average static charge from the measured static charges; and, wherein the micronized powder has been prepared according to a process comprising: (i) packaging the micronized powder, (ii) sterilizing the micronized powder, and (iii) filling the sterilized micronized powder into a container at a relative humidity of 30% to 40% at a temperature from 15° C. to 30° C.; mixing the micronized powder with a buffer solution to create a pharmaceutical composition; and administering the pharmaceutical composition to the subject in need of malaria treatment. 2. The method of claim 1, wherein the buffer solution is a bicarbonate buffer solution comprising sodium phosphate monobasic monohydrate, sodium phosphate dibasic dihydrate, sodium hydroxide, phosphoric acid, and water. 3. The method of claim 1, wherein the buffer solution has a pH in the range of about 7.9 to 8.1. 4. The method of claim 1, wherein the buffer solution contains phosphate ions in the range of about 0.25 to 0.35 M. 5. The method of claim 1, wherein the buffer solution is sterilized before the mixing. 6. The method of claim 1, wherein the pharmaceutical composition is administered via intravenous injection. 7. The method of claim 6, wherein the pharmaceutical composition is administered as a slow IV infusion. 8. The method of claim 7, wherein the pharmaceutical composition is administered as the slow IV infusion for a time up to 5 minutes. 9. The method of claim 1, wherein the pharmaceutical composition is administered to the subject in an amount ranging from about 1 mg/kg to 8 mg/kg. 10. The method of claim 1, wherein the pharmaceutical composition is intravenously administered to the subject in an amount ranging from about 2-3 mg/kg of body weight for at least three days. 11. The method of claim 1, wherein the pharmaceutical composition is intravenously administered to the subject in an amount of about 2.4 mg/kg. 12. The method of claim 11, wherein the pharmaceutical composition is intravenously administered to the subject for at least three days. 13. The method of claim 1, wherein the pharmaceutical composition is parenterally administered to the subject in an amount of about 10 mg/mL. 14. The method of claim 1, wherein the micronized powder absorbs moisture in an amount from about 0.01 wt % to 0.03 wt %, based on the total weight of the micronized powder. 15. The method of claim 1, wherein the micronized powder has an angle of repose of less than 40° when passing through a funnel with an opening of 8 mm to 12 mm. 16. The method of claim 1, wherein the micronized powder has a particle size possessing a D90 of less than 20 μm, a D100 of less than 100 μm, or a D50 of less than 5 μm. 17. The method of claim 1, wherein the artesunate or pharmaceutically acceptable salt thereof is free of Corynebacterium auris growth. 18. The method of claim 1, wherein the micronized powder comprises no more than about 0.5% water, no more than about 0.5% dihydroartemisinin, no more than about 0.2% didehydrodeoxyartemisinin, and no more than about 0.2% of other impurities. 19. The method of claim 1, wherein the micronized powder has a Hausner ratio of at least 1.6 when subjected to a relative humidity from about 30% to 40%. 20. The method of claim 1, wherein the crystalline form of artesunate or the pharmaceutically acceptable salt thereof is 10-α artesunate. 21. The method of claim 1, wherein the micronized powder has a bulk density below 0.2 g/mL. 22. The method of claim 1, wherein the micronized powder has a tap density above 0.3 g/mL. 23. The method of claim 1, wherein the packaging of the micronized powder comprises packing the micronized powder in at least three polyethylene containers. 24. The method of claim 1, wherein the sterilizing of the micronized powder comprises sterilizing the micronized powder with ethylene oxide.