Details for Patent: 6,673,335

Title:	Compositions and methods for the pulmonary delivery of aerosolized medicaments
Abstract:	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 .mu.m mass median diameter (MMD), usually 1.0-4.0 .mu.m MMD, and preferably 1.0-3.0 .mu.m 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 .mu.m mass median aerodynamic diameter (MMAD), usually 1.5-4.5 .mu.m MMAD, and preferably 1.5-4.0 .mu.m MMAD. Such compositions are of pharmaceutical grade purity.
Inventor(s):	Platz; Robert M. (Half Moon Bay, CA), Patton; John S. (San Carlos, CA), Foster; Linda (Sunnyvale, CA), Eljamal; Mohammed (San Jose, CA)
Assignee:	Nektar Therapeutics (San Carlos, CA)
Filing Date:	Jul 14, 2000
Application Number:	09/616,236
Claims:	1. An aerosolizable, spray-dried powder formulation for pulmonary delivery comprising a growth hormone and a pharmaceutically acceptable carrier, wherein the powder comprises a plurality of particles having an average particle size of less than about 10 microns MMD and further wherein each particle is comprised of the growth hormone and the carrier. 2. The formulation of claim 1, containing less than 5% growth hormone degradation products. 3. The formulation of claim 1, wherein said carrier is selected from the group consisting of carbohydrates, amino acids, polypeptides, and combinations thereof. 4. The formulation of claim 3, wherein said carrier is a carbohydrate selected from the group consisting of galactose, mannose, sorbose, lactose, trehalose, cyclodextrin, raffinose, maltodextrins, dextrans, mannitol, and xylitol. 5. The formulation of claim 3, wherein said carrier is an amino acid. 6. The formulation of claim 5, wherein said amino acid is selected from the group consisting of alanine, glycine, tryptophan, tyrosine, leucine, and phenylalanine. 7. The formulation of claim 5, wherein said amino acid is a hydrophobic amino acid. 8. The formulation of claim 5, wherein said amino acid is effective to increase the dispersibility of the formulation. 9. The formulation of claim 1, wherein said carrier comprises HSA. 10. The formulation of claim 1, wherein said carrier comprises a buffer. 11. The formulation of claim 1, comprising from about 0.05 to about 99 percent by weight growth hormone. 12. The formulation of claim 1, comprising a therapeutically effective amount of growth hormone. 13. The formulation of claim 3, comprising particles sized from about 1.0-5.0 microns MMD. 14. The formulation of claim 1, comprising particles sized from about 1.0-5.0 microns MMAD. 15. The formulation of claim 1, further characterized by a delivered dose of greater than about 30%. 16. A method of treating a disease state responsive to treatment by growth hormone, said method comprising administering by inhalation to a subject the formulation of claim 12 in aerosolized form. 17. The method of claim 16, wherein said disease state responsive to treatment by growth hormone comprises short stature. 18. The method of claim 16, wherein said disease state responsive to treatment by growth hormone comprises renal failure. 19. The method of claim 16, wherein the efficiency of systemic delivery of growth hormone by inhalation is from about 15 to about 50 percent. 20. The method of claim 16, wherein said administering step comprises dispersing said powder formulation in a gas stream to form an aerosol, capturing the aerosol in a chamber fitted with a mouthpiece, and inhaling. 21. The method of claim 20, wherein said powder is dispersed at a delivered dose of greater than 30%. 22. A method for preparing a growth hormone-based dry powder composition suitable for pulmonary delivery, said method comprising spray drying an aqueous solution of growth hormone and a pharmaceutically acceptable carrier under conditions effective to provide a respirable, spray dried powder, wherein the powder comprises a plurality of particles having an average particle size of less than about 10 microns MMD and further wherein each particle is comprised of the growth hormone and the carrier. 23. The method of claim 22, wherein the powder formed in said spray drying step contains less than 5% degradation products. 24. The method of claim 22, wherein the spray dried powder formed in said drying step comprises particles 98% or more of which have a diameter of 10 microns or less. 25. The method of claim 24, wherein the spray dried powder formed in said drying step comprises particles about 90% of which have a diameter of 5 microns or less. 26. A spray dried respirable powder produced by the method of claim 22.