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 (m mass median diameter (MMD), usually 1.0-4.0 (m MMD, and preferably 1.0-3.0 (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 (m mass median aerodynamic diameter (MMAD), usually 1.5-4.5 (m MMAD, and preferably 1.5-4.0 MMAD. Such composition are of pharmaceutical grade purity.

The subject matter claimed is:  
     
         1 . A dispersible pharmaceutical-based dry powder composition for pulmonary delivery, said composition comprising a therapeutically effective amount of the pharmaceutical in combination with a pharmaceutically acceptable carrier.  
     
     
         2 . The composition of  claim 1 , wherein the composition is substantially free from penetration enhancers.  
     
     
         3 . The composition of  claim 2 , wherein the carrier comprises HSA.  
     
     
         4 . The composition of  claim 3 , wherein the carrier further comprises a carbohydrate bulking agent.  
     
     
         5 . The composition of  claim 1 , wherein about 95% of the mass of the dry powder composition has a particle size of less than 10 μm.  
     
     
         6 . The composition of  claim 5 , wherein about 80% of the mass of the dry powder composition has a particle size of less than 5 μm.  
     
     
         7 . A unit dosage form for pulmonary delivery of a pharmaceutical, which dosage form comprises a unit dosage receptacle containing a dispersible pharmaceutical-based dry powder composition, which composition comprises a therapeutically effective amount of the pharmaceutical in combination with a pharmaceutically acceptable carrier.  
     
     
         8 . The unit dosage form of  claim 7  wherein the carrier comprises HSA and a carbohydrate bulking agent, the composition is substantially free from penetration enhancers and about 95% of the mass of the dry powder composition has a particle size of less than about 10 μm.  
     
     
         9 . A method of treating a disease state responsive to treatment by a pharmaceutical, which method comprises pulmonarily administering to a subject in need thereof a physiologically effective amount of a dispersible pharmaceutical-based dry powder composition that comprises a therapeutically effective amount of the macromolecule in combination with a pharmaceutically acceptable carrier.  
     
     
         10 . The method of  claim 9  wherein the carrier comprises HSA and a carbohydrate bulking agent, the composition is substantially free from penetration enhancers and about 95% of the mass of the dry powder composition has a particle size of less than about 10Am.  
     
     
         11 . A method for aerosolizing a pharmaceutical-based dry powder composition that comprises a therapeutically effective amount of the pharmaceutical in combination with a pharmaceutically acceptable carrier, which method comprises: 
 dispersing an amount of the dry powder composition in a gas stream to form an aerosol and    capturing the aerosol in a chamber suitable for subsequent inhalation by a patient.    
     
     
         12 . The method of  claim 11 , wherein the carrier comprises HSA and a carbohydrate bulking agent, the composition is substantially free from penetration enhancers and about 95% of the mass of the dry powder composition has a particle size of less than about 10 μm.  
     
     
         13 . A method for preparing a spray-dried, pharmaceutical-based dry powder composition that comprises a therapeutically effective amount of the macromolecule and a pharmaceutically acceptable carrier, which method comprises spray-drying an aqueous mixture of the macromolecule and the carrier under conditions to provide a respirable dry powder.  
     
     
         14 . The method of  claim 13  wherein the composition is substantially free from penetration enhancers.  
     
     
         15 . The method of  claim 14 , wherein the carrier comprises HSA.  
     
     
         16 . The method of  claim 15 , wherein the carrier further comprises a carbohydrate bulking agent.  
     
     
         17 . The method of  claim 16 , wherein the bulking agent is mannitol.  
     
     
         18 . The method of  claim 13 , wherein 95% of the mass of the spray-dry composition has a particle size less than 10 μm.  
     
     
         19 . A spray-dried, macromolecule-based dry powder composition for pulmonary delivery, said composition comprising a therapeutically effective amount of the macromolecule in combination with a pharmaceutically acceptable carrier that comprises HSA and a carbohydrate bulking agent, wherein the composition is substantially free from penetration enhancers and about 95% of the mass of the dry powder composition has a particle size of less than 10 μm.  
     
     
         20 . The composition of  claim 19 , wherein the bulking agent is mannitol.  
     
     
         21 . The composition according to any of claims  1 ,  7 ,  9 ,  13 , and  19  wherein the macromolecule is selected from the group comprising insulin, interlukin 1 receptor, parathyroid hormone (PTH-34), alpha-I antitrypsin, calcitonin, low molecular weight heparin, heparin, interferon, and nucleic acids.