Composition for pulmonary administration comprising a drug and a hydrophobic amino acid

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 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 . An aerosolizable, spray-dried powder formulation for pulmonary delivery comprising a therapeutically effective amount of FSH.  
     
     
         2 . The formulation of  claim 1 , containing less than 5% FSH degradation products.  
     
     
         3 . The formulation of  claim 1 , further comprising a pharmaceutically acceptable excipient.  
     
     
         4 . The formulation of  claim 3 , wherein said excipient is selected from the group consisting of carbohydrates, amino acids, polypeptides, buffers, and salts.  
     
     
         5 . The formulation of  claim 4 , wherein said excipient is a carbohydrate selected from the group consisting of galactose, mannose, sorbose, lactose, trehalose, cyclodextrin, raffinose, maltodextrins, dextrans, mannitol, and xylitol.  
     
     
         6 . The formulation of  claim 4 , wherein said excipient is an amino acid.  
     
     
         7 . The formulation of  claim 6 , wherein said amino acid is selected from the group consisting of alanine, glycine, tryptophan, tyrosine, leucine, and phenylalanine.  
     
     
         8 . The formulation of  claim 6 , wherein said amino acid is a hydrophobic amino acid.  
     
     
         9 . The formulation of  claim 8 , wherein said amino acid is effective to increase the dispersibility of the formulation.  
     
     
         10 . The formulation of  claim 4 , wherein said excipient comprises HSA.  
     
     
         11 . The formulation of  claim 4 , wherein said excipient comprises a buffer.  
     
     
         12 . The formulation of  claim 4 , comprising from about 0.05 to about 99 percent by weight FSH.  
     
     
         13 . The formulation of  claim 1 , wherein said powder comprises particles with an average particle of less than 10 microns MMD.  
     
     
         14 . The formulation of  claim 13 , comprising particles sized from about 1.0-5.0 microns MMD.  
     
     
         15 . The formulation of  claim 1  wherein said powder comprises particles sized from about 1.0-5.0 microns MMAD.  
     
     
         16 . The formulation of  claim 1 , further characterized by a delivered dose of greater than about 30%.  
     
     
         17 . The formulation of  claim 1 , aerosolizable in a dry powder inhaler.  
     
     
         18 . A method of treating a disease state responsive to treatment by FSH, said method comprising administering by inhalation to a subject in need thereof the formulation of  claim 1  in aerosolized form.  
     
     
         19 . The method of  claim 18 , wherein said administering step comprises dispersing said powder formulation in a gas stream to form an aerosol and inhaling.  
     
     
         20 . A method for preparing a FSH dry powder composition suitable for pulmonary delivery, said method comprising spray drying an aqueous mixture comprising FSH under conditions effective to provide a respirable, spray dried FSH powder.  
     
     
         21 . The method of  claim 20 , wherein the powder formed in said spray drying step contains less than 5% FSH degradation products.  
     
     
         22 . The method of  claim 20 , wherein said aqueous mixture further comprises a pharmaceutically acceptable excipient.  
     
     
         23 . The method of  claim 20 , wherein 98% or more of the mass of the spray dried powder comprises particles having a diameter of 10 microns or less.  
     
     
         24 . The method of  claim 20 , wherein 90% or more of the mass of the spray dried powder comprises particles having a diameter of 5 microns or less.  
     
     
         25 . A respirable powder produced by the method of  claim 20.