Inhalation drug delivery
Described here are unit dose containers, methods, and kits for treating asthma and other pulmonary conditions by nebulization. The unit doses of active agents are provided in a low volume formulation, which results in faster nebulization of the unit doses. The containers are also formed to minimize internal surface area so that effective re-dispersion of the active agents can be achieved while reducing adsorption to the walls of the containers.
1. A unit dose container for inhalation therapy comprising:
(a) a body having a cavity containing a liquid formulation therein, the cavity having a cavity wall and a wetted surface area of about 9.7 square centimeters or less; and
(b) a dispensing end in fluid communication with the cavity, wherein the convergence between the cavity and the dispensing end is smooth and continuous and wherein the dispensing end does not form a neck region with the body,
wherein the formulation comprises particles of an active agent.
2. The unit dose container of claim 1 wherein less than 20% of the active agent is adsorbed to the cavity wall.
3. The unit dose container of claim 1 wherein less than 15% of the active agent is adsorbed to the cavity wall.
4. The unit dose container of claim 1 , further comprising a frangible cap attached to the dispensing end.
5. The unit dose container of claim 1 , wherein the dispensing end has a diameter between about 0.5 cm to about 1.5 cm.
6. The unit dose container of claim 1 , wherein the cavity is configured to hold between about 50 μl to about 2.0 ml of the formulation.
7. The unit dose container of claim 6 , wherein the cavity is configured to hold about 0.5 ml to about 1.6 ml of the formulation.
8. The unit dose container of claim 7 , wherein the cavity is configured to hold about 1.6 ml of the formulation.
9. The unit dose container of claim 1 , wherein the active agent is selected from the group consisting of anti-infective agents, anti-inflammatory agents, chemotherapeutic agents, and combinations thereof.
10. The unit dose container of claim 9 , wherein the active agent comprises an anti-inflammatory agent.
11. The unit dose container of claim 10 , wherein the anti-inflammatory agent comprises a corticosteroid.
12. The unit dose container of claim 11 , wherein the corticosteroid comprises budesonide or a derivative or analogue thereof.
13. The unit dose container of claim 12 , wherein not more than about 0.17 mg of budesonide is adsorbed to the cavity wall.
14. The unit dose container of claim 1 , wherein the wetted surface area is less than about 6.44 square centimeters.
15. The unit dose container of claim 1 , wherein the wetted surface area is less than about 3.22 square centimeters.
16. The unit dose container of claim 1 , wherein the wetted surface area is less than about 1.61 square centimeters.
17. The unit dose container of claim 1 comprising a polymer selected from the group consisting of polycarbonate, polyethylene, low density polyethylene (LDPE), polyester, polystyrene, polypropylene, polysulfone, polyurethane, ethylene-vinyl-acetate, and combinations thereof.
18. The unit dose container of claim 17 , wherein the polymer comprises LDPE.
19. The unit dose container of claim 1 , wherein the formulation has a concentration of 0.135 mg per 1.5 ml of active agent, and the formulation is stored for up to 12 months at 25° C. and 40% relative humidity with no substantial agglomeration of the active agent particles.
20. The unit dose container of claim 19 , wherein the active agent particles have an average particle size of between about 400 nm to about 550 nm.
21. The unit dose container of claim 1 , wherein the formulation has a concentration of 0.250 mg per 1.5 ml, and the formulation is stored for up to 12 months at 25° C. and 40% relative humidity with no substantial agglomeration of the active agent particles.
22. The unit dose container of claim 21 , wherein the active agent particles have an average particle size of between about 400 nm to about 550 nm.
23. The unit dose container of claim 1 , wherein the formulation further comprises a surface active agent, a phospholipid, EDTA, or a combination thereof.
24. The unit dose container of claim 12 , wherein the formulation further comprises a surface active agent, a phospholipid, EDTA., or a combination thereof.
25. The unit dose container of claim 1 , wherein the container has a retention volume of less than about 6% of the fill volume.
26. The unit dose container of claim 1 , wherein the container has a retention volume of less than about 3% of the fill volume.