Devices, Compositions and Methods for the Pulmonary Delivery of Aerosolized Medicaments
According to the subject invention, dispersible dry powder pharmaceutical-based compositions are provided, including methods for their manufacture and dry powder dispersion devices. A dispersible dry powder pharmaceutical-based composition is one having a moisture content of less than about 10% by weight (% w) water, usually below about 5% w and preferably less than about 3% w; a particle size of about 1.0-5.0 μm mass median diameter (MMD), usually 1.0-4.0 μm MMD, and preferably 1.0-3.0 μm MMD; a delivered dose of about >30%, usually >40%, preferably >50%, and most preferred >60%; and an aerosol particle size distribution of about 1.0-5.0 μm mass median aerodynamic diameter (MMAD), usually 1.5-4.5 μm MMAD, and preferably 1.5-4.0 MMAD. Such composition are of pharmaceutical grade purity.
1 . A unit dosage comprising:
a unit dosage receptacle; and
a pharmaceutical composition within the unit dosage receptacle, wherein the pharmaceutical composition comprises a therapeutically effective amount of insulin and a buffer, and wherein the pharmaceutical composition comprises particles having a mass median aerodynamic diameter ranging from about 1 μm to 5 μm.
2 . The unit dosage of claim 1 , wherein the buffer comprises sodium citrate.
3 . The unit dosage of claim 1 , wherein the particles have an average particle size less than about 10 μm.
4 . The unit dosage of claim 1 , wherein about 95% of the mass is in particles having a diameter of about 10 μm or less, and about 80% of the mass is in particles having a diameter of less than 5 μm.
5 . The unit dosage of claim 1 , wherein more than about 98% of the mass is in particles having a diameter size less than 10 μm, and about 90% of the mass is in particles having a diameter less than 5 μm.
6 . The unit dosage of claim 1 , wherein the pharmaceutical composition comprises less than about 10 wt % water.
7 . The unit dosage of claim 1 , wherein the pharmaceutical composition comprises less than about 5 wt % water.
8 . The unit dosage of claim 1 , wherein the pharmaceutical composition comprises less than about 3 wt % water.
9 . The unit dosage of claim 1 , wherein an amount of the insulin ranges from about 0.2 wt % to 97.0 wt % of the pharmaceutical composition.
10 . The unit dosage of claim 1 , wherein the therapeutically effective amount ranges from about 0.5 mg to 15 mg.
11 . The unit dosage of claim 1 , wherein the unit dosage receptacle comprises a capsule.
12 . The unit dosage of claim 1 , wherein the unit dosage receptacle comprises a foil plastic laminate.
13 . The unit dosage of claim 1 , wherein the pharmaceutical composition comprises less than about 10 wt % water, and wherein the unit dosage receptacle comprises a capsule.
14 . The unit dosage of claim 1 , wherein the particles have an average particle size less than about 10 μm, wherein the pharmaceutical composition comprises less than about 10 wt % water, and wherein the unit dosage receptacle comprises a capsule.
15 . The unit dosage of claim 1 , wherein the buffer comprises sodium citrate, wherein the pharmaceutical composition comprises less than about 10 wt % water, and wherein the unit dosage receptacle comprises a capsule.
16 . The unit dosage of claim 1 , wherein the buffer comprises sodium citrate, wherein the pharmaceutical composition comprises less than about 10 wt % water, and wherein the unit dosage receptacle comprises a foil plastic laminate.
17 . The unit dosage of claim 1 , wherein the particles have an average particle size less than about 10 μm, wherein the buffer comprises sodium citrate, wherein the pharmaceutical composition comprises less than about 10 wt % water, and wherein the unit dosage receptacle comprises a foil plastic laminate.
18 . An inhalation device, wherein the unit dosage receptacle of claim 1 is within the inhalation device.
19 . A unit dosage comprising:
a unit dosage receptacle; and
a pharmaceutical composition within the unit dosage receptacle, wherein the pharmaceutical composition comprises a therapeutically effective amount of insulin and a penetration enhancer, and wherein the pharmaceutical composition comprises particles having a mass median aerodynamic diameter ranging from about 1 μm to 5 μm.
20 . The unit dosage of claim 19 , wherein the particles have an average particle size less than about 10 μm.
21 . The unit dosage of claim 19 , wherein about 95% of the mass is in particles having a diameter of about 10 μm or less, and about 80% of the mass is in particles having a diameter of less than 5 μm.
22 . The unit dosage of claim 19 , wherein more than about 98% of the mass is in particles having a diameter size less than 10 μm, and about 90% of the mass is in particles having a diameter less than 5 μm.
23 . The unit dosage of claim 19 , wherein the pharmaceutical composition comprises less than about 10 wt % water.
24 . The unit dosage of claim 19 , wherein the pharmaceutical composition comprises less than about 5 wt % water.
25 . The unit dosage of claim 19 , wherein the pharmaceutical composition comprises less than about 3 wt % water.
26 . The unit dosage of claim 19 , wherein an amount of the insulin ranges from about 0.2 wt % to 97.0 wt % of the pharmaceutical composition.
27 . The unit dosage of claim 19 , wherein the therapeutically effective amount ranges from about 0.5 mg to 15 mg.
28 . The unit dosage of claim 19 , wherein the unit dosage receptacle comprises a capsule.
29 . The unit dosage of claim 19 , wherein the unit dosage receptacle comprises a foil plastic laminate.
30 . The unit dosage of claim 19 , wherein the pharmaceutical composition comprises less than about 10 wt % water, and wherein the unit dosage receptacle comprises a capsule.
31 . The unit dosage of claim 19 , wherein the particles have an average particle size less than about 10 μm, wherein the pharmaceutical composition comprises less than about 10 wt % water, and wherein the unit dosage receptacle comprises a capsule.
32 . The unit dosage of claim 19 , wherein the pharmaceutical composition comprises less than about 10 wt % water, and wherein the unit dosage receptacle comprises a foil plastic laminate.
33 . The unit dosage of claim 19 , wherein the particles have an average particle size less than about 10 μm, wherein the pharmaceutical composition comprises less than about 10 wt % water, and wherein the unit dosage receptacle comprises a foil plastic laminate.
34 . An inhalation device, wherein the unit dosage receptacle of claim 19 is within the inhalation device.
35 . A unit dosage comprising:
a unit dosage receptacle; and
a pharmaceutical composition within the unit dosage receptacle, wherein the pharmaceutical composition comprises a therapeutically effective amount of insulin, wherein the pharmaceutical composition comprises less than about 10 wt % water, and wherein the pharmaceutical composition comprises particles having a mass median aerodynamic diameter ranging from about 1 μm to 5 μm.
36 . The unit dosage of claim 35 , wherein the particles have an average particle size less than about 10 μm.
37 . The unit dosage of claim 35 , wherein about 95% of the mass is in particles having a diameter of about 10 μm or less, and about 80% of the mass is in particles having a diameter of less than 5 μm.
38 . The unit dosage of claim 35 , wherein more than about 98% of the mass is in particles having a diameter size less than 10 μm, and about 90% of the mass is in particles having a diameter less than 5 μm.
39 . The unit dosage of claim 35 , wherein the pharmaceutical composition comprises less than about 5 wt % water.
40 . The unit dosage of claim 35 , wherein the pharmaceutical composition comprises less than about 3 wt % water.
41 . The unit dosage of claim 35 , wherein an amount of the insulin ranges from about 0.2 wt % to 97.0 wt % of the pharmaceutical composition.
42 . The unit dosage of claim 35 , wherein the therapeutically effective amount ranges from about 0.5 mg to 15 mg.
43 . The unit dosage of claim 35 , wherein the unit dosage receptacle comprises a capsule.
44 . The unit dosage of claim 35 , wherein the unit dosage receptacle comprises a foil plastic laminate.
45 . The unit dosage of claim 35 , wherein the pharmaceutical composition comprises less than about 5 wt % water, and wherein the unit dosage receptacle comprises a capsule.
46 . The unit dosage of claim 35 , wherein the particles have an average particle size less than about 10 μm, wherein the pharmaceutical composition comprises less than about 5 wt % water, and wherein the unit dosage receptacle comprises a capsule.
47 . The unit dosage of claim 35 , wherein the pharmaceutical composition comprises less than about 5 wt % water, and wherein the unit dosage receptacle comprises a foil plastic laminate.
48 . The unit dosage of claim 35 , wherein the particles have an average particle size less than about 10 μm, wherein the pharmaceutical composition comprises less than about 5 wt % water, and wherein the unit dosage receptacle comprises a foil plastic laminate.
49 . An inhalation device, wherein the unit dosage receptacle of claim 35 is within the inhalation device.
50 - 76 . (canceled)