INHALABLE SUSTAINED THERAPEUTIC FORMULATIONS
The present invention is based, in part, on the unexpected discovery that particles for pulmonary delivery of a therapeutic, prophylactic or diagnostic agent that comprise a phospholipid and a sufficient amount of leucine can produce sustained effect of the agent. Specifically, particles for pulmonary delivery of a therapeutic, prophylactic or diagnostic agent that contain a phospholipid or combination of phospholipids, wherein the phospholipid or combination of phospholipids is present in the particles in an amount of about 1 to 46 weight percent; and leucine, wherein leucine is present in the particles in an amount of at least 46 weight percent, can contribute to sustained effect of the agent. Particles that comprise at least 46 weight percent leucine but that do not contain phospholipids do not exhibit these same sustained effect properties.
1 . Non-polymeric particles for pulmonary delivery of a therapeutic, prophylactic ordiagnostic agent, the particles comprising:
(a) a therapeutic, prophylactic or diagnostic agent;
(b) a phospholipid or combination of phospholipids, wherein the phospholipidor combination of phospholipids is present in the particles in an amount of about 1 to 46 weight percent; and
(c) leucine, wherein leucine is present in the particles in an amount of at least 46 weight percent,
said particles having a tap density of less than about 0.4 g/cm 3 .
2 . The particles of claim 1 , wherein the particles have a tap density less than or equal to about 0.3 g/cm 3 .
3 . The particles of claim 1 , wherein the particles have a tap density less than or equal to about 0.2 g/cm 3 .
4 . The particles of claim 1 , wherein the particles have a tap density less than or equal to about 0.1 g/cm 3 .
5 . The particles of claim 1 , wherein the particles have a tap density less than or equal to 25 about 0.05 g/cm 3 .
6 . The particles of claim 1 , wherein the particles have a mean geometric diameter of about 5 to 30 microns.
7 . The particles of claim 6 , wherein the particles have a mean geometric diameter of about 9 to 30 microns.
8 . The particles of claim 1 , wherein the particles have an aerodynamic diameter of about 1 to 5 microns.
9 . The particles of claim 8 , wherein the particles have an aerodynamic diameter of about 1 to 3 microns.
10 . The particles of claim 8 , wherein the particles have an aerodynamic diameter of about 3 to 5 microns.
11 . The particles of claim 1 further comprising a compound selected from the group consisting of polysaccharides, sugars, amino acids, proteins, lipids, surfactants, cholesterol, fatty acids, fatty acid esters, buffer salts and any combination thereof.
12 . The particles of claim 1 , wherein the particles comprise about 5 to 10 weight percent of the therapeutic, prophylactic or diagnostic agent.
13 . The particles of claim 1 , wherein the particles comprise about 8 weight percent of the therapeutic, prophylactic or diagnostic agent.
14 . The particles of claim 1 , wherein the therapeutic, prophylactic or diagnostic agent is albuterol or a salt thereof.
15 . The particles of claim 1 , wherein the therapeutic, prophylactic or diagnostic agent is salmeterol or a salt thereof.
16 . The particles of claim 1 , wherein the therapeutic, prophylactic or diagnostic agent is estrone or a salt thereof.
17 . The particles of claim 1 , wherein the therapeutic, prophylactic or diagnostic agent is a protein or peptide.
18 . The particles of claim 1 , wherein the therapeutic, prophylactic or diagnostic agent is hydrophilic.
19 . The particles of claim 1 , wherein the therapeutic, prophylactic or diagnostic agent is hydrophobic.
20 . The particles of claim 1 , wherein the particles comprise about 46 weight percent phospholipid or combination of phospholipids.
21 - 58 . (canceled)