Monovalent metal cation dry powders for inhalation

Abstract

The present invention is directed toward respirable dry powders and particles for systemic delivery of pharmaceutically active agents or delivery to the respiratory tract. The dry powders contain one or more monovalent metal cations (such as Na + ), are small and dispersible.

What is claimed is: 
     
         1 . A respirable dry powder comprising respirable dry particles comprising sodium chloride in an amount of about 61% to about 90%, leucine in an amount of about 5% to about 30%, and one or more pharmaceutically active agents, wherein the sodium chloride, leucine and one or more pharmaceutically active agents amount to 100%, wherein all percentages are weight percentages on a dry basis, and wherein the respirable dry powder comprising respirable dry particles are characterized by a volume median geometric diameter (VMGD) at 1 bar as measured using a HELOS/RODOS system of about 1 micron to about 5 microns, a dispersibility ratio (1/4 bar) of less than 1.5, and a tap density of about 0.4 g/cubic centimeter (cm 3 ) to about 1.2 g/cm 3 . 
     
     
         2 . The respirable powder of  claim 1 , wherein the respirable dry powder comprising respirable dry particles have a Fine Particle Fraction (FPF) of less than 5.6 microns of at least 45%. 
     
     
         3 . The respirable dry powder of  claim 1 , wherein the respirable dry powder comprising respirable dry particles have a mass median aerodynamic diameter (MMAD) of about 5 microns or less. 
     
     
         4 . The respirable dry powder of  claim 1 , wherein the respirable dry powder comprising respirable dry particles have a tap density of about 0.45 g/cm 3  to about 1.2 g/cm 3 . 
     
     
         5 . The respirable dry powder of  claim 1 , wherein the one or more pharmaceutically active agents are selected from the group consisting of an antibiotic, a long-acting beta2-agonists (LABA), a long-acting muscarinic antagonists (LAMA), a corticosteroid, and any combination thereof. 
     
     
         6 . The respirable dry powder of  claim 1 , wherein the one or more pharmaceutically active agents are one or more macromolecules. 
     
     
         7 . The respirable dry powder of  claim 6 , wherein the one or more macromolecules are selected from the group consisting of a cytokine, a chemokine, a growth factor, a hormone, and an antibody. 
     
     
         8 . The respirable dry powder of  claim 1 , wherein the respirable dry powder comprising respirable dry particles are further characterized by a capsule emitted powder mass (CEPM) of at least 80% when emitted from a passive dry powder inhaler with a total inhalation energy of about 1.2 Joules. 
     
     
         9 . The respirable dry powder of  claim 1 , wherein the respirable dry powder comprising respirable dry particles are further characterized by a volume median diameter (Dv50) of less than 5 micrometers when emitted from a passive dry powder inhaler with a total inhalation energy of about 1.2 Joules. 
     
     
         10 . A method for treating a respiratory disease comprising administering to the respiratory tract of a patient in need thereof an effective amount of the respirable dry powder of  claim 1 . 
     
     
         11 . The method of  claim 10 , wherein the respiratory disease is asthma, airway hyperresponsiveness, seasonal allergic allergy, bronchiectasis, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or cystic fibrosis. 
     
     
         12 . A method for treating or preventing an acute exacerbation of a respiratory disease comprising administering to the respiratory tract of a patient in need thereof an effective amount of the respirable dry powder of  claim 1 . 
     
     
         13 . The method of  claim 12 , wherein the respiratory disease is asthma, airway hyperresponsiveness, seasonal allergic allergy, bronchiectasis, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, or cystic fibrosis. 
     
     
         14 . The method of  claim 12 , wherein the acute exacerbation is caused by one or more infections selected from the group consisting of a viral infection, a bacterial infection, a fungal infection and a parasitic infection. 
     
     
         15 . A method for treating or preventing an infectious disease of the respiratory tract comprising administering to the respiratory tract of a patient in need thereof an effective amount of the respirable dry powder of  claim 1 . 
     
     
         16 . The method of  claim 15 , wherein the infectious disease is caused by one or more infections selected from the group consisting of a viral infection, a bacterial infection, a fungal infection and a parasitic infection.