Composition for pulmonary administration comprising a drug and a hydrophobic amino acid
View Patent ↗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 μm MMAD. Such compositions are of pharmaceutical grade purity.
1. A dispersible dry powder composition for pulmonary delivery, said composition comprising a therapeutically effective amount of a drug and a hydrophobic amino acid, Wherein about 95% of the mass of the dry powder composition has a particle size of less than 10 μm.
2. The dry powder composition of claim 1 , further comprising a pharmaceutically acceptable carrier.
3. The dry powder composition of claim 1 , wherein the hydrophobic amino acid is selected from the group consisting of tryptophan, tyrosine, leucine, and phenylalanine.
4. The dry powder composition of claim 1 , substantially free from penetration enhancers.
5. The dry powder composition of claim 2 , wherein the carrier comprises human serum albumin.
6. The dry powder composition of claim 2 , wherein the carrier comprises a carbohydrate bulking agent.
7. The dry powder composition of claim 1 , wherein about 80% of the mass of the dry powder composition has a particle size of less than 5 μm.
8. The dry powder composition of claim 1 , wherein the drug is a macromolecule.
9. The dry powder composition of claim 1 , wherein the drug is a non-macromolecule.
10. The dry powder composition of claim 3 , wherein said hydrophobic amino acid is lecuine.
11. The dry powder composition of claim 1 , wherein said dry powder composition particles having an aerosol particle size distribution of from about 1.0 to 5.0 μm MMAD.
12. The dry powder composition of claim 1 , wherein the dry powder is characterized by a delivered dose of greater than about 30%.
13. The dry powder composition of claim 8 , wherein the macromolecule is selected from the group consisting of insulin, interleukin 1 receptor, parathyroid hormone, alpha-1 antitrypsin, calcitonin, interferon, low molecular weight heparin, and nucleic acids.
14. A unit dosage form for pulmonary delivery of a pharmaceutical drug, said unit dosage form comprising a dispersible dry powder composition, comprising a therapeutically effective amount of the pharmaceutical drug in combination with a hydrophobic amino acid according to any one of claims 1 , 2 , 3 , 10 , or 11 .
15. A spray-dried, dispersible dry powder composition for pulmonary delivery, said composition comprising a therapeutically effective amount of a drug and a hydrophobic amino acid, where about 95% of the mass of the dry powder composition has a particle size of less than 10 μm.