Monovalent Metal Cation Dry Powders

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.

1 . A respirable dry powder comprising respirable dry particles that comprise sodium sulfate, mannitol, an active agent, wherein said active agent is a P38 kinase inhibitor, and an optional excipient; wherein the respirable dry powder comprising respirable dry particles is characterized by a volume median geometric diameter (VMGD) at 1 bar as measured using a HELOS/RODOS system between 0.5 microns and 5 microns, a tap density of greater than 0.4 g/cc to about 1.2 g/cc, and a dispersibility ratio of 1 bar/4 bar of about 1.5 or less. 
     
     
         2 - 63 . (canceled) 
     
     
         64 . The respirable dry powder of  claim 1 , wherein the sodium sulfate is present in an amount between about 20% and about 60%, wherein the weight percentages are on a dry basis of the respirable dry particles. 
     
     
         65 . The respirable dry powder of  claim 1 , wherein the sodium sulfate is present in an amount between about 61% and about 90%, wherein the weight percentages are on a dry basis of the respirable dry particles. 
     
     
         66 . The respirable dry powder of  claim 1 , wherein the mannitol is present in an amount of about 50% or less, wherein the weight percentage is on a dry basis of the respirable dry particles. 
     
     
         67 . The respirable dry powder of  claim 1 , wherein the mannitol is present in an amount between about 51% to about 80%, wherein the weight percentage is on a dry basis of the respirable dry particles. 
     
     
         68 . The respirable dry powder of  claim 1 , wherein the p38 kinase inhibitor is present in an amount of 5% or more, wherein the weight percentage is on a dry basis of the respirable dry particles. 
     
     
         69 . The respirable dry powder of  claim 1 , wherein the active agent is present in an amount between about 50% and about 99.9%, wherein the weight percentages are on a dry basis of the respirable dry particles. 
     
     
         70 . The respirable dry powder of  claim 1 , wherein said active agent inhibits p38 and Syk. 
     
     
         71 . A method of treating a pulmonary disease comprising administering to the respiratory tract of a patient in need thereof an effective amount of the respirable dry powder of  claim 1 . 
     
     
         72 . The method of  claim 71 , wherein the pulmonary disease is asthma, airway hyperresponsiveness, seasonal allergic allergy, bronchiectasis, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, cystic fibrosis, cancer or idiopathic pulmonary fibrosis. 
     
     
         73 . A method of treating acute exacerbation of a pulmonary disease comprising administering to the respiratory tract of a patient in need thereof an effective amount of the respirable dry powder of  claim 1 . 
     
     
         74 . The method of  claim 73 , wherein the pulmonary disease is pulmonary disease is asthma, airway hyperresponsiveness, seasonal allergic allergy, bronchiectasis, chronic bronchitis, emphysema, chronic obstructive pulmonary disease, cystic fibrosis, cancer or idiopathic pulmonary fibrosis.