Capsules containing high doses of levodopa for pulmonary use
View Patent ↗The present invention provides a capsule containing an inhalable powder composition wherein the composition comprises about 75% by weight or more levodopa, dipalmitoylphosphatidylcholine (DPPC) and a salt characterized by a working density of less than about 100 g/L. The invention further provides a capsule containing an inhalable powder composition wherein the composition comprises about 75% by weight or more levodopa, dipalmitoylphosphatidylcholine (DPPC) and a salt characterized by a working density of less than about 100 g/L wherein the capsule material comprises hydroxypropylmethylcellulose (HPMC) and titanium dioxide.
1. A capsule for use in an inhalation device filled with a dry powder comprising levodopa and having a working density between about 0.02 to about 0.1 g/cm 3 , and containing a capsule shell comprising hydroxypropyl methylcellulose (HPMC) and titanium dioxide, and
wherein said capsule emits more powder comprising levodopa upon actuation of the inhalation device as compare to a capsule that comprises HPMC and is free of titanium dioxide.
2. The capsule of claim 1 , wherein said working density is between about 0.02 g/cm 3 to about 0.05 g/cm 3 .
3. The capsule of claim 1 , wherein said dry powder comprises from about 2 to about 8% of water by weight.
4. The capsule of claim 3 , wherein said dry powder comprises from about 5 to about 6% of water by weight.
5. The capsule of claim 1 , wherein said capsule is a 00 size capsule.
6. The capsule of claim 5 , wherein said dry powder comprises between about 15 and 50 milligrams of levodopa.
7. The capsule of claim 6 , wherein said dry powder comprises between about 25 and 35 milligrams of levodopa.
8. The capsule of claim 1 , wherein said dry powder further comprises a salt.
9. The capsule of claim 8 , wherein said salt is sodium chloride.
10. The capsule of claim 8 , wherein said dry powder further comprises a phospholipid.
11. The capsule of claim 10 , wherein said phospholipid is dipalmitoylphosphatidylcholine (DPPC).
12. The capsule of claim 1 comprising from about 25 to 45 milligrams of dry powder comprising at least 80% of levodopa by weight, a fine particle fraction (FPF) between 55 to 68% of the nominal dose, and a working density between about 0.02 to about 0.05 g/cm 3 .
13. The capsule of claim 1 , wherein the dry powder comprises about 85% by weight or more of levodopa.
14. The capsule of claim 1 , wherein the dry powder comprises about 90% by weight or more of levodopa.
15. The capsule of claim 1 , wherein the dry powder comprises a salt and the salt is sodium chloride (NaCl).
16. The capsule of claim 1 , wherein the FPF of the dry powder is about 50% to about 70% of the nominal dose.
17. The capsule of claim 1 , wherein the capsule is filled with about 20 milligrams or more of the dry powder.
18. The capsule of claim 1 , wherein the capsule is filled with about 30 to about 50 milligrams of dry powder.
19. The capsule of claim 1 , wherein the dry powder composition comprises a weight ratio of levodopa/DPPC/NaCl of 90:8:2.
20. The capsule of claim 1 , wherein the dry powder comprises about 75% by weight or more levodopa, DPPC and a salt.
21. The capsule of claim 1 , wherein the FPF of the dry powder is about 50% to about 70% of the nominal dose.