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.

1 . 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 solution, wherein the first fluid component comprises a protein that is incompatible with the second fluid component;    atomizing the mixed fluid solution flowing out of the static mixer to produce droplets, wherein the atomizing step is carried out using an atomizer that comprises an internal mixing nozzle; and    drying the droplets in a dryer to form dry particles, wherein the dry particles contain less than about 6% of soluble dimer of the protein and have a Fine Particle Fraction (FPF (3.3)) in the range of about 57-66.    
     
     
         2 . The method of  claim 1 , wherein the atomizing step is performed immediately after the combining step.  
     
     
         3 . The method of  claim 1 , wherein the protein is insulin.  
     
     
         4 . The method of  claim 2 , wherein the protein is insulin.  
     
     
         5 . The method of  claim 1 , further comprising adding a surfactant to the first fluid component, the second fluid component, or the mixed fluid solution.  
     
     
         6 . The method of  claim 3 , further comprising: adding DPPC to the first fluid component, the second fluid component, or the mixed fluid solution.  
     
     
         7 . The method of  claim 1 , wherein the nozzle is a six-hole nozzle.  
     
     
         8 . The method of  claim 3 , wherein the nozzle is a six-hole nozzle.  
     
     
         9 . The method of  claim 1 , wherein a solids concentration of the mixed fluid solution is more than about 2 g/L.  
     
     
         10 . The method of  claim 9 , wherein the solids concentration of the mixed fluid solution is more than about 5 g/L.  
     
     
         11 . The method of  claim 10 , wherein the solids concentration of the mixed fluid solution is less than about 60 g/L.  
     
     
         12 . The method of  claim 11 , wherein the solids concentration of the mixed fluid solution is less than about 30 g/L.  
     
     
         13 . The method of  claim 1 , further comprising adding about 5-40 g/L ammonium bicarbonate to the first fluid component, the second fluid component, or the mixed fluid solution.  
     
     
         14 . The method of  claim 1 , wherein the second fluid component is an organic solution comprising approximately 60-70% water by volume and wherein the mixed fluid solution comprises approximately 20% organic phase by volume.  
     
     
         15 . The method of  claim 14 , wherein the second fluid component is an organic solution comprising approximately 60% water by volume and wherein the mixed fluid solution comprises approximately 20% organic phase by volume.  
     
     
         16 . The method of  claim 1 , wherein the drying step is performed in a dryer with an outlet temperature of 35-70° C.  
     
     
         17 . The method of  claim 16 , wherein the outlet temperature is approximately 45° C.  
     
     
         18 . The method of  claim 1 , 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.    
     
     
         19 . The method of  claim 1 , wherein the atomizing step comprises using an atomization gas rate of approximately 35-120 g/min.  
     
     
         20 . The method of  claim 19 , wherein the atomization gas rate is approximately 120 g/min.  
     
     
         21 . The method of  claim 1 , wherein the atomizing step comprises using a liquid feed rate of approximately 10-75 mL/min.  
     
     
         22 . The method of  claim 21 , wherein the liquid feed rate is approximately 10-20 mL/min.  
     
     
         23 . The method of  claim 1 , wherein the drying step is performed using a drying gas rate of approximately 80-125 kg/hr.  
     
     
         24 . The method of  claim 1 , wherein the drying gas rate is approximately 110 kg/hr.