Pulmonary delivery of a fluoroquinolone

Abstract

A composition for pulmonary administration comprises a fluoroquinolone betaine, such as ciprofloxacin betaine, and an excipient. In one version, the particles have a mass median aerodynamic diameter from about 1 μm to about 5 μm, and the fluoroquinolone has a half life in the lungs of at least 1.5 hours. The composition is useful in treating an endobronchial infection, such as Pseudomonas aeruginosa, and is particularly useful in treating cystic fibrosis.

What is claimed is: 
     
         1 . A powder composition for pulmonary administration in a unit dose receptacle, the powder composition comprising:
 particles comprising a fluoroquinolone in zwitterionic form and an excipient, wherein the fluoroquinolone comprises one or more of cinofloxacin, enoxacin, norfloxacin, ofloxacin, levofloxacin and moxifloxacin,   wherein the particles have a mass median aerodynamic diameter from about 1 μm to about 5 μm and wherein the particles have a rugosity of from about 3 to 10.   
     
     
         2 . A composition according to  claim 1  wherein the excipient comprises a phospholipid. 
     
     
         3 . A composition according to  claim 1  wherein the composition comprises from 50% to 70% fluoroquinolone, from 15% to 35% phospholipid, and from 1% to 3% metal ion containing material. 
     
     
         4 . A composition according to  claim 1  wherein the fluoroquinolone is in crystalline form. 
     
     
         5 . A composition according to  claim 1  wherein the composition in the unit dose receptacle comprises at least about 10 mg of fluoroquinolone. 
     
     
         6 . A composition according to  claim 1  wherein the particles have a bulk density of less than 0.6 g/cm 3 . 
     
     
         7 . A composition according to  claim 1  wherein the unit dose receptacle comprises a capsule. 
     
     
         8 . A composition according to  claim 7  wherein the receptacle contains a therapeutic dose of the composition effective for treating a bacterial infection. 
     
     
         9 . A composition according to  claim 7  wherein the receptacle contains a therapeutic dose of the composition effective for treating non-CF bronchiectasis, chronic obstructive pulmonary disease, pneumonia or chronic bronchitis. 
     
     
         10 . A composition according to  claim 7  in combination with a dry powder aerosolization apparatus. 
     
     
         11 . A composition and apparatus according to  claim 10  wherein the dry powder aerosolization apparatus is adapted to aerosolize the composition within the apparatus by the flow of air through the apparatus. 
     
     
         12 . A composition according to  claim 10  wherein the composition provides an emitted dose in the passive dry powder inhaler of at least about 50%. 
     
     
         13 . A powder composition for pulmonary administration, the powder composition comprising:
 particles comprising from 50% to 70% fluoroquinolone in zwitterionic form and from 15% to 35% phospholipid, wherein the fluoroquinolone comprises one or more of cinofloxacin, enoxacin, norfloxacin, ofloxacin, levofloxacin and moxifloxacin; and   wherein the particles have a mass median aerodynamic diameter from about 1 μm to about 5.   
     
     
         14 . A composition according to  claim 13  wherein the fluoroquinolone is in crystalline form. 
     
     
         15 . A composition according to  claim 13  wherein the composition comprises from 1% to 3% metal ion containing material. 
     
     
         16 . A composition according to  claim 13  wherein the composition has a rugosity of from about 3 to 10. 
     
     
         17 . A composition according to  claim 13  in a unit dose receptacle wherein the mass of the composition in the unit dose receptacle is sufficient to provide at least about a 10 mg dose to the lungs. 
     
     
         18 . A composition according to  claim 17  wherein the receptacle contains a therapeutic dose of the composition effective for treating a bacterial infection. 
     
     
         19 . A composition according to  claim 17  wherein the receptacle contains a therapeutic dose of the composition effective for treating non-CF bronchiectasis, chronic obstructive pulmonary disease, pneumonia or chronic bronchitis.