Pulmonary delivery particles with phospholipid structural matrix

Abstract

A pulmonary delivery medicament comprises a plurality of particulates, each particulate having a perforated microstructure comprising a phospholipid structural matrix and active agent, the phospholipid structural matrix comprising greater than about 50% w/w phospholipid, and the particulates having a geometric diameter of from 0.5 to 50 μm. The medicament can be made from a liquid feedstock having greater than about 20% w/w phospholipid with an added active agent, which is spray dried to produce the particulates.

1 . A pulmonary delivery medicament comprising: 
 a plurality of particulates, the particulates having a perforated microstructure comprising a phospholipid structural matrix and active agent, the phospholipid structural matrix comprising greater than about 50% w/w phospholipid, and the particulates having a geometric diameter of from 0.5 to 50 μm.    
     
     
         2 . A medicament according to  claim 1  wherein the phospholipid structural matrix comprises greater than about 70% w/w phospholipid.  
     
     
         3 . A medicament according to  claim 1  wherein the phospholipid structural matrix comprises greater than about 80% w/w phospholipid.  
     
     
         4 . A medicament according to  claim 1  wherein the phospholipid structural matrix comprises greater than about 95% w/w phospholipid.  
     
     
         5 . A medicament according to  claim 1  wherein the phospholipid comprises one or more of dipalmitoylphosphatidylcholine, disteroylphosphatidylcholine, diarachidoylphosphatidylcholine dibehenoylphosphatidylcholine, diphosphatidyl glycerol, short-chain phosphatidylcholines, long-chain saturated phosphatidylethanolamines, long-chain saturated phosphatidylserines, long-chain saturated phosphatidylglycerols, and long-chain saturated phosphatidylinositols.  
     
     
         6 . A medicament according to  claim 1  wherein the particulates have a mass median diameter of less than 10 μm.  
     
     
         7 . A medicament according to  claim 1  wherein the particulates have a bulk density of less than 0.5 g/cm 3 .  
     
     
         8 . A medicament according to  claim 1  wherein the active agent is water insoluble.  
     
     
         9 . A medicament according to  claim 8  wherein the water insoluble active agent comprises a fungicide.  
     
     
         10 . A medicament according to  claim 1  wherein the active agent is crystalline.  
     
     
         11 . A medicament according to  claim 1  wherein the particulates comprise an inorganic salt.  
     
     
         12 . A medicament according to  claim 1  wherein the particulates comprise calcium.  
     
     
         13 . A medicament according to  claim 1  wherein the particulates are formed by spray drying a liquid feedstock.  
     
     
         14 . A medicament according to  claim 13  wherein the liquid feedstock is absent a blowing agent.  
     
     
         15 . A method of making a medicament for pulmonary delivery, the method comprising: 
 (a) forming a liquid feedstock comprising greater than about 20% w/w phospholipid;    (b) adding an active agent to the liquid feedstock; and    (c) spray drying the liquid feedstock to form a plurality of particulates, the particulates having a perforated microstructure comprising a phospholipid structural matrix and active agent, the phospholipid structural matrix comprising greater than about 50% w/w phospholipid, and the particulates having a geometric diameter of from 0.5 to 50 μm.    
     
     
         16 . A method according to  claim 15  comprising forming particulates having a perforated microstructure comprising a phospholipid structural matrix comprising greater than about 70% w/w phospholipid.  
     
     
         17 . A method according to  claim 15  wherein (b) comprises providing a water insoluble active agent to the liquid feedstock, and (c) comprises spray drying the liquid feedstock.  
     
     
         18 . A method according to  claim 17  wherein the water insoluble active agent is crystalline.  
     
     
         19 . A method according to  claim 15  wherein (b) comprises adding an inorganic salt to the liquid feedstock.  
     
     
         20 . A method according to  claim 19  wherein the inorganic salt comprises calcium.