Dry powder inhaler formulations comprising surface-modified particles with anti-adherent additives

Abstract

The present invention is concerned with a refinement of the processing of particles that are to form a dry powder formulation which is to be administered to the lung using a dry powder inhaler (DPI) device. In particular, the present invention provides the processing of particles of active material and particles of carrier material in the presence of additive material to provide a powder composition which exhibits excellent powder properties and which is economical to produce.

1 . A powder formulation comprising an active, magnesium stearate and lactose, wherein the powder formulation incorporates magnesium stearate on the surface of both the active particles and the lactose particles, and wherein when the magnesium stearate is added to the lactose, the amount used is from 0.5 to 2 wt % of the weight of the lactose. 
     
     
         2 . The powder formulation according to  claim 1 , wherein magnesium stearate forms a discontinuous coating on the surfaces of the active and lactose particles. 
     
     
         3 . The powder formulation according to  claim 1 , wherein the powder formulation has a tapped density of at least 0.1 g/cc. 
     
     
         4 . The powder formulation according to  claim 1 , wherein the active is a bronchodilator. 
     
     
         5 . The powder formulation according to  claim 1  which is a passive device powder formulation. 
     
     
         6 . The powder formulation according to  claim 1 , wherein, when the magnesium stearate is added to the active, the amount used is in the range of 0.1 to 50 wt % of the weight of the active. 
     
     
         7 . The powder formulation according to  claim 1 , wherein, when the magnesium stearate is added to the active, the amount used is in the range of 1 to 20 wt % of the weight of the active. 
     
     
         8 . The powder formulation according to  claim 1 , wherein the lactose particles have a median diameter of about 3 to about 40 μm. 
     
     
         9 . A dry powder inhaler device comprising a powder formulation according to  claim 1 , wherein the device is a passive device. 
     
     
         10 . A method for producing a powder formulation, the method comprising co-milling active particles with magnesium stearate, separately co-milling lactose particles with magnesium stearate, and combining the co-milled active and co-milled lactose particles, wherein the amount of magnesium stearate added to the lactose is from 0.5 to 2 wt % of the weight of the lactose. 
     
     
         11 . The method according to  claim 10 , wherein active particles and lactose particles are co-milled using different milling processes. 
     
     
         12 . The method according to  claim 10 , wherein the magnesium stearate forms a discontinuous coating on the surfaces of the active particles and lactose particles. 
     
     
         13 . The method according to  claim 10 , wherein the powder formulation has a tapped density of at least 0.1 g/cc. 
     
     
         14 . The method according to  claim 10 , wherein the active particles are a bronchodilator. 
     
     
         15 . The method according to  claim 10 , wherein, when the magnesium stearate is added to the active particles, the amount used is in the range of 0.1 to 50 wt % of the weight of the active. 
     
     
         16 . The method according to  claim 10 , wherein, when the magnesium stearate is added to the active particles, the amount used is in the range of 1 to 20 wt % of the weight of the active. 
     
     
         17 . The method according to  claim 10 , wherein the lactose particles have a median diameter of about 3 to about 40 μm.