Reactor for producing pharmaceutical particles in a precipitation process

Abstract

Reactors, reactor systems and methods for producing particles in a precipitation process are provided. The reactor includes a housing defining a reaction chamber, a stator assembly including two or more stators, a rotor assembly including two or more rotors, the rotor assembly configured for rotation about an axis of rotation relative to the stator assembly, a first inlet to supply a first reactant material to the reaction chamber at a first radial location, a second inlet to supply a second reactant material to the reaction chamber at a second radial location different from the first radial location, wherein the first and second reactant materials react to produce precipitation of particles in the reaction chamber, and an outlet to supply the particles formed in the reaction chamber.

1 . A continuous process for making a dry powder for pulmonary inhalation comprising:
 preparing a first solution comprising an acid in a vessel;   preparing a second solution comprising a diketopiperazine and ammonium hydroxide or sodium hydroxide having a pH value greater than about 10;   feeding the first solution and the second solution at a predetermined flow rate and temperature to a reactor having a reaction chamber and including a stator assembly having two or more stators and a rotor assembly having two or more rotors; wherein the first solution and the second solution meet upon entry into the reaction chamber;   forming a precipitate comprising microparticles of the diketopiperazine within the reaction chamber, and   collecting the microparticles downstream from the reactor.   
     
     
         2 . The continuous process of  claim 1 , further comprising feeding a third solution or a fourth solution into the reaction chamber. 
     
     
         3 . The continuous process of  claim 2 , wherein the third solution or the fourth solution comprises deionized water. 
     
     
         4 . The continuous process of  claim 1 , wherein the diketopiperazine has the formula: 
       
         
           
           
               
               
           
         
       
     
     
         5 . The continuous process of  claim 1 , wherein the first solution and the second solution are pumped into the reaction chamber at a flow rate in an acid to base ratio of from about 0.8 to about 1.2. 
     
     
         6 . The continuous process of  claim 1 , wherein feeding the first solution and the second solution comprises pumping said first solution and said second solution so that the first solution and the second solution meet at an entrance to the reaction chamber. 
     
     
         7 . The continuous process of  claim 1 , wherein the first solution or the second solution predetermined flow rate is from about 10 kg/min to about 100 kg/min. 
     
     
         8 . The continuous process of  claim 1 , wherein the process is carried out in the reaction chamber at a pressure ranging from about 15 psig to about 2,000 psig. 
     
     
         9 . The continuous process of  claim 1 , wherein the temperature of the first solution and the second solution in the reaction chamber is from about 10° C. to about 30° C. 
     
     
         10 . The continuous process of  claim 1 , wherein the first solution or the second solution comprises a surfactant. 
     
     
         11 . The continuous process of  claim 10 , wherein the surfactant is polysorbate 80. 
     
     
         12 . The continuous process of  claim 1 , further comprising washing the precipitate in deionized water. 
     
     
         13 . A dry powder for pulmonary inhalation made by the process according to  claim 1 .