Dry powder formulations for inhalation
A respirable dry powder including acetylsalicylic acid in particles has a mass median aerodynamic diameter (MMAD) within a range of about 0.5 μm to about 10 μm. The respirable dry powder may contain a pharmaceutically acceptable excipient, such as a phospholipid, in an amount ranging from about 0.1% (w/w) to about 10% (w/w) of the particles.
1. A dry powder composition comprising dry particles that comprise acetylsalicylic acid or a pharmaceutically acceptable salt thereof in an amount of 50% (w/w) or more of the composition, wherein the dry particles have a mass median aerodynamic diameter (MMAD) within a range of 0.5 μm to 5 μm, wherein said dry particles have a DV50 in a range of 3 μm to 6.7 μm and a DV10 in a range of 0.9 μm to 3.3 μm, wherein the composition further comprises one or more phospholipids in an amount ranging from 0.1% (w/w) to 10% (w/w) of the composition, and wherein the MMAD varies less than about 10% after the dry powder composition is stored at 30° C. at 65% relative humidity for about 4 weeks.
2. The dry powder composition of claim 1 , wherein the MMAD varies less than about 8% after the dry powder composition is stored at 30° C. at 65% relative humidity for about 4 weeks.
3. The dry powder composition of claim 1 , wherein the MMAD varies less than about 6% after the dry powder composition is stored at 30° C. at 65% relative humidity for about 4 weeks.
4. The dry powder composition of claim 1 , wherein the composition comprises particles having an MMAD size distribution such that said particles exhibit a DV90 less than about 20 μm, a DV50 in a range of 3 μm to 6.7 μm, and a DV10 in a range of 0.9 μm to 2 μm.
5. The dry powder composition of claim 1 , wherein the composition comprises particles having an MMAD size distribution such that said particles exhibit a DV90 less than about 10 μm, a DV50 in a range of 3 μm to 4 μm, and a DV10 in a range of 0.9 μm to 1 μm.
6. The dry powder composition of claim 1 , wherein the composition comprises particles having an MMAD size distribution such that said particles exhibit a DV90 less than about 6 μm.
7. The dry powder composition of claim 1 , wherein the composition comprises particles having an MMAD size distribution such that said particles exhibit a DV50 in a range of 3 μm to 5 μm, and a DV10 in a range of 0.9 μm to 2 μm.
8. The dry powder composition of claim 1 , wherein the composition comprises particles having an MMAD size distribution such that said particles exhibit a DV50 in a range of 3 μm to 4 μm, and a DV10 in a range of 0.9 μm to 1.5 μm.
9. The dry powder composition of claim 4 , wherein the DV90, DV50 and/or DV10 vary less than about 10% after the dry powder composition is stored at 30° C. at 65% relative humidity for about 4 weeks.
10. The dry powder composition of claim 1 , wherein the composition comprises particles coated with a pharmaceutically acceptable excipient.
11. The dry powder composition of claim 10 , wherein the pharmaceutically acceptable excipient is a phospholipid.
12. The dry powder composition of claim 1 , wherein the phospholipid is dipalmitoyl phosphatidylcholine (DPPC), distearoyl phosphatidylcholine (DSPC), soy lecithin or a combination thereof.
13. The dry powder composition of claim 1 , wherein the phospholipid is in an amount ranging from 1% fw/w) to 5% (w/w) of the composition.
14. The dry powder composition of claim 1 , wherein the phospholipid is DSPC in an amount of about 5% (w/w) of the composition.
15. The dry powder composition of claim 1 , wherein phospholipid is soy lecithin in an amount of about 0.1% (w/w) of the composition.
16. The dry powder composition of claim 1 , wherein the MMAD ranges from about 2.0 to about 5.0 μm.
17. The dry powder composition of claim 1 , wherein the MMAD ranges from about 3.0 to about 4.0 μm.
18. A dry powder composition comprising dry particles that comprise acetylsalicylic acid or a pharmaceutically acceptable salt thereof in an amount of 50% (w/w) or more of the composition, wherein the dry particles have a mass median aerodynamic diameter (MMAD) within a range of 0.5 μm to 5 μm, wherein said dry particles have a DV50 in a range of 3 μm to 6.7 μm and a DV10 in a range of 0.9 μm to 3.3 μm, wherein the composition further comprises one or more phospholipids in an amount ranging from 0.1% (w/w) to 10% (w/w) of the composition, and wherein the MMAD varies less than about 10% after the dry powder composition is stored at 50° C. at 75% relative humidity for about 2 weeks.
19. A dry powder composition comprising dry particles that comprise acetylsalicylic acid or a pharmaceutically acceptable salt thereof in an amount of 50% (w/w) or more of the composition, wherein the dry particles have a mass median aerodynamic diameter (MMAD) within a range of 0.5 μm to 5 μm, wherein said dry particles have a DV50 in a range of 3 μm to 6.7 μm and a DV10 in a range of 0.9 μm to 3.3 μm, wherein the composition further comprises one or more phospholipids in an amount ranging from 0.1% (w/w) to 10% (w/w) of the composition, and wherein the MMAD varies less than about 10% after the dry powder composition is stored at 50° C. for about 5 days.
20. A drug delivery system effective to reduce the risk of a thromboembolic event or treat thrombosis, wherein the system comprises the dry powder composition of claim 1 , and wherein acetylsalicylic acid is present at a dose ranging from about 5 mg to about 40 mg.
21. The drug delivery system of claim 20 , further comprising clopidogrel.
22. The drug delivery system of claim 20 , wherein mass percent of stages in an NGI testing apparatus of the respirable powder yields are at, stage 1 about 10% to about 13%, stage 2, about 20% to about 23%, stage 3, about 13% to about 15%, and stage 4, about 5% to about 6% and fine particle fraction ranges from about 45% to about 55%.
23. The drug delivery system of claim 20 , wherein mass percent of stages in an NGI testing apparatus of the respirable powder yields are at, stage 1 about 5% to about 10%, stage 2, about 10% to about 18%, stage 3, about 15% to about 20%, and stage 4, about 10% to about 15% and fine particle fraction ranges from about 50% to about 70%.
24. The drug delivery system of claim 20 , further comprising an excipient.
25. The drug delivery system of claim 24 , wherein the excipient is sodium lauryl sulfate (SLS), lactose, starch, cellulose, leucine, sodium citrate, maltodextrin and/or mannitol.
26. A method of treating an ischemic event, reducing the risk of a thromboembolic event or treating thrombosis, comprising, administrating to a subject in need thereof a therapeutically effective dose of the dry powder composition of claim 1 .
27. The method of claim 26 , wherein the thromboembolic event is a myocardial infraction.
28. The method of claim 26 , wherein the thromboembolic event is a transient ischemic event.
29. The method of claim 26 , wherein the thromboembolic event is a stroke.
30. The method of claim 26 , wherein the thromboembolic event is treated within about 5 minutes of onset of the ischemic event.
31. The method of claim 26 , wherein the thromboembolic event is treated within about 10 minutes of onset of the ischemic event.
32. The method of claim 26 , wherein the thromboembolic event is treated within about 15 minutes of onset of the ischemic event.