Claims for Patent: 12,121,506

Summary for Patent: 12,121,506

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:	US18/443,850
Patent Claims:	1. 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 −0.05 kV to 0.05 kV according to a static charge test that includes: (i) subjecting the powder to a relative humidity of 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, wherein the micronized powder has been prepared according to a process comprising: (i) packaging the micronized powder into at least three polyethylene fiber containers, (ii) sterilizing the micronized powder with ethylene oxide while packaged in the at least three polyethylene fiber containers, 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. 2. The powder of claim 1, wherein the powder absorbs moisture in an amount from 0.01 wt % to 0.03 wt %, based on the total weight of the powder, when subjected to a relative humidity from 30% to 40%. 3. The powder of claim 2, wherein the powder has an angle of repose of less than 40° when passing through a funnel with an opening of 8 mm to 12 mm at a relative humidity from 30% to 40%. 4. The powder of claim 3, wherein the powder is micronized to 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. 5. The powder of claim 4, wherein the artesunate or pharmaceutically acceptable salt thereof is free of Corynebacterium auris growth. 6. The powder of claim 5, wherein the powder comprises no more than 0.5% water, no more 0.5% dihydroartemisinin, no more 0.2% didehydrodeoxyartemisinin, and no more 0.2% of other impurities. 7. The powder of claim 6, wherein the powder has a Hausner ratio of at least 1.6 when subjected to a relative humidity from 30% to 40%. 8. The powder of claim 7, wherein the crystalline form of artesunate or the pharmaceutically acceptable salt thereof is 10-α artesunate. 9. The powder of claim 8, wherein the powder has a bulk density below 0.2 g/mL when subjected to a relative humidity from 30% to 40%. 10. The powder of claim 9, wherein the powder has a tap density above 0.3 g/mL when subjected to a relative humidity from 30% to 40%. 11. The micronized powder according to claim 1, further comprising a buffer solution. 12. The pharmaceutical composition of claim 11, wherein the buffer solution is a phosphate buffer solution. 13. The pharmaceutical composition of claim 12, wherein the phosphate buffer solution includes sodium phosphate monobasic monohydrate, sodium phosphate dibasic dihydrate, sodium hydroxide, phosphoric acid and water. 14. A process for the preparation of the powder as defined in claim 1, the process comprising: micronizing a raw artesunate ingredient into an artesunate powder, packaging the micronized powder Into at least three polyethylene fiber containers, sterilizing the micronized powder with ethylene oxide while packaged in the at least three polyethylene fiber containers, and filling the sterilized micronized powder Into a container at a relative humidity of 30% to 40% at a temperature of from 15° C. to 30° C. 15. The process of claim 14, wherein the filing the sterilized artesunate powder occurs under aseptic conditions. 16. The process of claim 14, wherein the filling of the sterilized artesunate powder is performed with a dosing system equipped with a dosing head having an opening of at least 2.5 mm. 17. The process of claim 16, wherein the sterilized artesunate powder is pre-mixed in the dosing head of the dosing system before being filled into a container. 18. The process of claim 17, wherein the container is a depyrogenated borosilicate clear glass vial.