Particulate drug-containing products and method of manufacture

Abstract

Provided is a compressed anti-solvent technique for manufacture of drug-containing powders for pulmonary delivery. The drug is processed in a cosolvent system including two or more mutually soluble organic solvents. Also provided are powders manufacturable by the manufacture method, including powders of substantially pure drug and powders including a biocompatible polymer for pulmonary sustained drug release applications. Also provided are packaged products including drug-containing powder in a container that is receivable by and operable with a dry powder inhaler to produce an aerosol including dispersed drug-containing particles when the inhaler is actuated.

1 - 45 . (canceled)  
   
   
       46 . A particulate product for pulmonary delivery of a drug, comprising: 
 a powder batch of particles including at least one drug, the powder batch having a tap density of from 0.1 to 0.5 grams per cubic centimeter and being aerosizable by an inhaler to produce an aerosol having dispersed particles comprising the drug and being suspended in a carrier gas, the dispersed particles having a mass median aerodynamic diameter of smaller than about 6 microns.    
   
   
       47 . The particulate product of  claim 46 , wherein the mass median aerodynamic diameter is smaller than about 5 microns.  
   
   
       48 . The particulate product of  claim 46 , wherein the mass median aerodynamic diameter is smaller than about 4 microns.  
   
   
       49 . The particulate product of  claim 46 , wherein at least some of the particles of the powder batch are large particle units having an envelope diameter of at least 10 microns, the powder batch being aerosizable in the inhaler to break apart at least a portion of the large particle units to produce at least a portion of the dispersed particles in the aerosol.  
   
   
       50 . The particulate product of  claim 49 , wherein the large particle units have an envelope diameter of larger than about 25 microns.  
   
   
       51 . The particulate product of  claim 49 , wherein the large particle units have an envelope diameter of larger than about 50 microns.  
   
   
       52 . The particulate product of  claim 49 , wherein the large particle units are substantially not spherical in shape.  
   
   
       53 . The particulate product of  claim 46 , wherein the drug comprises a member selected from the group consisting of peptides, proteins and genetic material.  
   
   
       54 . The particulate product of  claim 46 , wherein the drug comprises insulin.  
   
   
       55 . The particulate product of  claim 46 , wherein the powder batch is contained within a receptacle receivable by the inhaler, the receptacle being adapted to operate with the inhaler so, that when the receptacle is received by the inhaler, the inhaler is actuatable to aerosolize the powder batch from the receptacle to produce the aerosol.  
   
   
       56 . The particulate product of  claim 55 , wherein the powder batch is sized to include only a unit dose of the drug.  
   
   
       57 . The particulate product of  claim 56 , wherein the receptacle comprises a plurality of containers each containing a different one of said powder batch, the inhaler being successively actuatable to successively aerosolize each said powder batch.  
   
   
       58 . The particulate product of  claim 55 , wherein the powder batch is in the form of a substantially dry powder.  
   
   
       59 . The particulate product of  claim 46 , wherein the particles of the powder batch are dispersed in a propellant fluid and contained within the inhaler, the inhaler being actuatable to permit the propellant fluid to expand to produce a single dose aerosol.  
   
   
       60 . A method for generating an aerosol for pulmonary delivery of drug comprising aerosolization of the particulate product of  claim 46  to produce the aerosol of  claim 46 .  
   
   
       61 . An apparatus for generating a drug-containing aerosol for pulomary delivery of a drug, comprising: 
 an inhaler having disposed therein the particulate product of  claim 46 , the inhaler being actuabtable to aerosolize the powder batch to produce the aerosol of  claim 46 .    
   
   
       62 . The inhaler of  claim 61 , wherein the powder batch is in the form of a substantially dry powder.  
   
   
       63 . The inhaler of  claim 61 , wherein the inhaler is a dry powder inhaler.  
   
   
       64 - 93 . (canceled)