Methods and apparatus for making particles using spray dryer and in-line jet mill

Abstract

Methods and apparatus are provided for making particles comprising: (a) spraying an emulsion, solution, or suspension, which comprises a solvent and a bulk material (e.g., a pharmaceutical agent), through an atomizer and into a primary drying chamber, having a drying gas flowing therethrough, to form droplets comprising the solvent and bulk material dispersed in the drying gas; (b) evaporating, in the primary drying chamber, at least a portion of the solvent into the drying gas to solidify the droplets and form particles dispersed in drying gas; and (c) flowing the particles and at least a portion of the drying gas through a jet mill to deagglomerate or grind the particles. By coupling spray drying with “in-line” jet milling, a single step process is created from two separate unit operations, and an additional collection step is advantageously eliminated. The one-step, in-line process has further advantages in time and cost of processing.

1 . A method for making microparticles for use in diagnostic imaging, the method comprising: 
 (a) spraying an emulsion, solution, or suspension, which comprises a solvent and a bulk material which includes a synthetic polymer, through at least one atomizer and into a primary drying chamber having a drying gas inlet, a discharge outlet, and a drying gas flowing therethrough, to form droplets comprising the solvent and the bulk material, wherein the droplets are dispersed in the drying gas;    (b) evaporating, in the primary drying chamber, at least a portion of the solvent into the drying gas to solidify the droplets and form microparticles dispersed in the drying gas, the microparticles dispersed in the drying gas being a feedstream; and    (c) flowing the feedstream through an in-line, fluid energy impact mill to deagglomerate or grind the microparticles.    
     
     
         2 . The method of  claim 1 , wherein, before step (c), the feedstream of step (b) is directed through a particle concentration means to separate and remove between 50 and 100 vol. % of the drying gas from the feedstream.  
     
     
         3 . The method of  claim 1 , further comprising, before step (c), flowing the feedstream through a secondary drying chamber in fluid communication with the discharge outlet of the primary drying chamber to evaporate a second portion of the solvent into the drying gas.  
     
     
         4 . The method of  claim 1 , wherein step (c) is conducted to deagglomerate at least a portion of agglomerated microparticles, if any, while substantially maintaining the size and morphology of the individual microparticles.  
     
     
         5 . The method of  claim 1 , wherein the emulsion, solution, or suspension of step (a) further comprises a volatile salt, and the microparticles formed in step (b) have voids or pores therein.  
     
     
         6 . The method of  claim 1 , further comprising loading the porous microparticles with a perfluorocarbon gas.  
     
     
         7 . The method of  claim 1 , wherein the microparticles formed in step (b) have a volume average diameter between 2 and 50 μm.  
     
     
         8 . A method for making microparticles containing a drug, the method comprising: 
 (a) spraying an emulsion, solution, or suspension, which comprises a solvent and a bulk material which includes a therapeutic or prophylactic agent, through at least one atomizer and into a primary drying chamber having a drying gas inlet, a discharge outlet, and a drying gas flowing therethrough, to form droplets comprising the solvent and the bulk material, wherein the droplets are dispersed in the drying gas;    (b) evaporating, in the primary drying chamber, at least a portion of the solvent into the drying gas to solidify the droplets and form microparticles dispersed in the drying gas, the microparticles dispersed in the drying gas being a feedstream; and    (c) flowing the feedstream through an in-line, fluid energy impact mill to deagglomerate or grind the microparticles.    
     
     
         9 . The method of  claim 8 , wherein the bulk material further comprises a synthetic polymer.  
     
     
         10 . The method of  claim 8 , wherein, before step (c), the feedstream of step (b) is directed through a particle concentration means to separate and remove between 50 and 100 vol. % of the drying gas from the feedstream.  
     
     
         11 . The method of  claim 8 , further comprising, before step (c), flowing the feedstream through a secondary drying chamber in fluid communication with the discharge outlet of the primary drying chamber to evaporate a second portion of the solvent into the drying gas.  
     
     
         12 . The method of  claim 8 , wherein step (c) is conducted to deagglomerate at least a portion of agglomerated microparticles, if any, while substantially maintaining the size and morphology of the individual microparticles.  
     
     
         13 . The method of  claim 8 , wherein the emulsion, solution, or suspension of step (a) further comprises a volatile salt, and the microparticles formed in step (b) have voids or pores therein.  
     
     
         14 . The method of  claim 8 , wherein the microparticles formed in step (b) have a volume average diameter between 2 and 50 μm.  
     
     
         15 . The method of  claim 8 , wherein the therapeutic or prophylactic agent is a hydrophobic drug.