Method and formulation for inhalation

Abstract

This invention relates to drug delivery and in particular to the delivery of biologically active agents in the form of dry powders for inhalation. The invention also relates to methods for preparing such dry powder formulations and methods for their use.

The claims defining the invention are as follows: 
     
         1 . A method for preparing a dry powder for inhalation comprising:
 preparing an aqueous solution and/or suspension comprising a biologically active protein or peptide, one or more mono, di- or polysaccharides and/or amino acids capable of forming an amorphous glass matrix, and L-leucine; and   spray drying the aqueous solution or suspension to produce a dry powder suitable for inhalation.   
     
     
         2 . A method according to  claim 1  wherein the L-leucine is present in an amount of from 5 to 50% by weight based on the dry weight of the powder. 
     
     
         3 . A method of  claim 2  wherein the L-leucine is present in an amount of from 10 to 40% by weight. 
     
     
         4 . A method according to  claim 1  wherein
 the biologically active peptide or protein is oxytocin and/or an oxytocin derivative. 
 
     
     
         5 . A method according to  claim 1  wherein the one or more mono, di or polysaccharides and/or amino acids capable of forming an amorphous glass matrix comprises D-mannitol and glycine. 
     
     
         6 . A method according to  claim 1  wherein the spray drying is carried out at a temperature below 80° C. 
     
     
         7 . A dry powder formulation comprising:
 a biologically active protein or peptide,   an amorphous glass matrix comprising one or more mono, di- or polysaccharides and/or amino acids, and   L-leucine.   
     
     
         8 . A dry powder formulation according to  claim 7  wherein at least a portion of the L-leucine is located at the surface of the particles of the dry powder. 
     
     
         9 . A method for the treatment or prevention of a disease or condition comprising administering by inhalation a dry powder formulation according to  claim 8 . 
     
     
         10 . A method according to  claim 9  wherein the biologically active protein or peptide is oxytocin and/or an oxytocin derivative. 
     
     
         11 . A method according to  claim 10  wherein the disease or condition is selected from post partum haemorrhage, psychiatric diseases or conditions, cancer, pain, lactation and fertility disorders, sexual dysfunction, or conditions involving lack of trust or bonding. 
     
     
         12 . A method according to  claim 10  wherein the disease or condition is postpartum haemorrhage. 
     
     
         13 . A method according to  claim 12  wherein said dry powder is inhaled into the pulmonary system via the mouth. 
     
     
         14 . A method according to  claim 12  wherein the dry powder is inhaled nasally. 
     
     
         15 . A dry powder according to  claim 7  for inhalation comprising oxytocin and/or a derivative thereof, and a pulmonary acceptable carrier, wherein more than 40% of the particles of the dry powder upon inhalation have an aerodynamic diameter of less than 5 μm. 
     
     
         16 . A dry powder according to  claim 15  wherein the pulmonary acceptable carrier comprises one or more mono-, di- or polysaccharides and/or amino acids capable of forming in amorphous glass matrix. 
     
     
         17 . A dry powder according to  claim 15  wherein the pulmonary acceptable carrier comprises an inert polymer capable of forming an amorphous glass matrix. 
     
     
         18 . A dry powder according to  claim 17  wherein the pulmonary acceptable carrier comprises L-Leucine. 
     
     
         19 . A method of  claim 9  for the treatment or prevention of post partum haemorrhage comprising administering an effective amount of a dry powder to a subject in need thereof, wherein
 the dry powder comprises oxytocin and/or a derivative thereof, and a pulmonary acceptable carrier, wherein more than 40% of the particles of the dry powder upon inhalation have an aerodynamic diameter of less than 5 μm, wherein 
 
       the pulmonary acceptable carrier comprises one or more mono-, di- or polysaccharides and/or amino acids capable of forming in amorphous glass matrix and wherein, the pulmonary acceptable carrier comprises L-Leucine. 
     
     
         20 - 21 . (canceled)