Method and apparatus for producing dry particles

Abstract

Method and apparatus for producing dry particles. Two liquid components are combined in a static mixer, atomized into droplets, and the droplets dried to form dry particles. Use of the static mixer enables incompatible liquid components to be rapidly and homogeneously combined. The present invention optimizes process conditions for increasing and controlling particle porosity. The present invention also allows for optimization of particle size in real-time during particle production.

What is claimed is:  
     
         1 . A method for preparing a dry powder composition, comprising: 
 combining a first fluid component and a second fluid component in a mixer to form a mixed fluid, wherein the first fluid component comprises an active agent that is incompatible with the second fluid component;    atomizing the mixed fluid to produce droplets, wherein the atomizer comprises an internal mixing nozzle; and    drying the droplets to form dry particles,    wherein the dry particles contain less than about 6% high molecular weight protein and more than about 90% readily extractable protein product.    
     
     
         2 . The method of  claim 1 , wherein the atomizing step is performed immediately after the combining step.  
     
     
         3 . A method for preparing a dry powder composition, comprising: 
 combining a first fluid component and a second fluid component in a static mixer to form a mixed fluid, wherein the first fluid component comprises an active agent that is incompatible with the second fluid component;    atomizing the mixed fluid to produce droplets, wherein the atomizer comprises an internal mixing nozzle; and    drying the droplets to form dry particles.    
     
     
         4 . The method of any of claims  1  or  3 , wherein the first fluid component is hydrophilic and the second fluid component is hydrophobic and the combining step comprises adding the first fluid component to the second fluid component.  
     
     
         5 . The method of any of claims  1  or  3 , wherein the nozzle is a single-hole nozzle.  
     
     
         6 . The method of any of claims  1  or  3 , wherein the nozzle is a six-hole nozzle.  
     
     
         7 . The method of any of claims  1  or  3 , wherein the nozzle comprises a mixing chamber, and a liquid feed inlet to the mixing chamber, wherein the liquid feed inlet is positioned at an angle to a longitudinal axis of the nozzle to thereby generate a thin sheet of liquid in the mixing chamber.  
     
     
         8 . The method of any of claims  1  or  3 , further comprising adding a surfactant to the first fluid component, the second fluid component, or the mixed fluid.  
     
     
         9 . The method of  claim 8 , wherein the surfactant comprises a non-ionic surfactant.  
     
     
         10 . The method of  claim 8 , wherein the surfactant comprises DPPC.  
     
     
         11 . The method of  claim 8 , wherein the surfactant comprises Tween 80.  
     
     
         12 . The method of  claim 11 , wherein the adding step is carried out using greater than 0.2 wt % of Tween 80.  
     
     
         13 . The method of  claim 11 , wherein the adding step is carried out using about 0.2-2.8 wt % of Tween 80.  
     
     
         14 . The method of any of claims  1  or  3 , wherein a solids concentration of the mixed fluid is more than about 2 g/L.  
     
     
         15 . The method of  claim 14 , wherein the solids concentration of the mixed fluid is more than about 5 g/L.  
     
     
         16 . The method of  claim 15 , wherein the solids concentration of the mixed fluid is less than about 60 g/L.  
     
     
         17 . The method of  claim 16 , wherein the solids concentration of the mixed fluid is less than about 30 g/L.  
     
     
         18 . The method of any of claims  1  or  3 , further comprising adding about 5-40 g/L ammonium bicarbonate to the first fluid component, the second fluid component, or the mixed fluid.  
     
     
         19 . The method of any of claims  1  or  3 , wherein the second fluid component is an organic solution comprising approximately 60-70% water by volume and wherein the mixed fluid comprises approximately 20% organic phase by volume.  
     
     
         20 . The method of  claim 19 , wherein the second fluid component is an organic solution comprising approximately 60% water by volume and wherein the mixed fluid comprises approximately 20% organic phase by volume.  
     
     
         21 . The method of any of claims  1  or  3 , wherein the drying step is performed in a dryer with an outlet temperature of 35-70° C.  
     
     
         22 . The method of  claim 21 , wherein the outlet temperature is approximately 40° C.  
     
     
         23 . The method of  claim 21 , wherein the outlet temperature is approximately 60° C.  
     
     
         24 . The method of any of claims  1  or  3 , further comprising: 
 ascertaining an amount of solid ingredients necessary to achieve a solution concentration;  
 ascertaining an amount of liquid ingredients necessary to achieve the solution concentration;  
 combining the liquid ingredients and the solid ingredients to form the first fluid component.  
 
     
     
         25 . The method of any of claims  1  or  3 , wherein the atomizing step comprises using an atomization gas rate of approximately 35-120 g/min.  
     
     
         26 . The method of  claim 25 , wherein the atomization gas rate is approximately 45-80 g/min.  
     
     
         27 . The method of any of claims  1  or  3 , wherein the atomizing step comprises using a liquid feed rate of approximately 10-75 mL/min.  
     
     
         28 . The method of  claim 27 , wherein the liquid feed rate is approximately 15-40 mL/min.  
     
     
         29 . The method of any of claims  1  or  3 , wherein the drying step is performed using a drying gas rate of approximately 80-125 kg/hr.  
     
     
         30 . The method of any of claims  1  or  3 , wherein the liquid feed/drying gas ratio is approximately 5 to 60 mL liq/kg gas.  
     
     
         31 . An apparatus for preparing a dry powder composition, comprising: 
 a static mixer operative to combine a first fluid component with a second fluid component to form a mixed fluid, wherein the first fluid component comprises an active agent that is incompatible with the second fluid component;    an atomizer in fluid communication with the static mixer, whereby the mixed fluid is atomized to form droplets and wherein the atomizer comprises an internal mixing nozzle; and    a dryer, wherein the droplets are dried to form dry particles.    
     
     
         32 . The apparatus of  claim 31 , wherein the nozzle is a single-hole nozzle.  
     
     
         33 . The apparatus of  claim 31 , wherein the nozzle is a six-hole nozzle.  
     
     
         34 . The apparatus of  claim 31 , wherein the nozzle comprises a mixing chamber, and a liquid feed inlet to the mixing chamber, wherein the liquid feed inlet is positioned at an angle to a longitudinal axis of the nozzle to thereby generate a thin sheet of liquid in the mixing chamber.