Acoustic mixing for auto granulation

Abstract

A process for acoustically mixing a bulk drug substance involves the application of acoustic energy to drive an accelerative force in a mixing vessel containing the drug substance. The drug substance may be, for example, Elagolix.

1 . A process comprising acoustically mixing a bulk drug substance wherein said acoustic mixing comprises the application of acoustic energy to drive an accelerative force in a mixing vessel containing the drug substance. 
     
     
         2 . The process according to  claim 1  wherein said acoustic mixing comprises the application of an accelerative force to the mixing vessel of greater than 10 G force. 
     
     
         3 . The process of  claim 4  wherein said accelerative force is greater than 20 G. 
     
     
         4 . The process of  claim 5  wherein said accelerative force is greater than 40 G. 
     
     
         5 . The process of  claim 6  wherein said accelerative force is greater than 60 G. 
     
     
         6 . The process of  claim 7  wherein said accelerative force is greater than 80 G. 
     
     
         7 . The process according to  claim 1  wherein said drug substance comprises an amorphous solid. 
     
     
         8 . The process according to  claim 1  wherein said drug substance has a flowability constant of less than 5. 
     
     
         9 . The process according to  claim 1  wherein said drug substance has a flowability constant of less than 2. 
     
     
         10 . The process according to  claim 1  wherein prior to acoustic mixing, the drug substance has a flowability constant of less than 2 and subsequent to mixing greater than 2. 
     
     
         11 . The process according to  claim 1  wherein prior to acoustic mixing, the drug substance has a flowability constant of less than 1 and subsequent to mixing greater than 1. 
     
     
         12 . The process according to  claim 1  wherein the flowability constant is increased by at least 0.1. 
     
     
         13 . The process according to  claim 1  wherein the flowability constant is increased by at least 0.2. 
     
     
         14 . The process according to  claim 1  wherein the flowability constant is increased by at least 0.3. 
     
     
         15 . The process according to  claim 1  wherein the flowability constant is increased by at least 0.4. 
     
     
         16 . The process according to  claim 1  wherein the flowability constant is increased by at least 0.5. 
     
     
         17 . The process according to  claim 1  wherein prior to acoustic mixing said drug substance has a bulk density of less than 0.4 g/ml. 
     
     
         18 . The process according to  claim 1  wherein prior to acoustic mixing, the drug substance has a volume-averaged particle size DV10 of less than 100 um. 
     
     
         19 . The process according to  claim 1  wherein acoustic mixing of the drug substance increases the volume-averaged particle size DV10 by at least 10 um. 
     
     
         20 . The process according to  claim 1  wherein said drug substance is elagolix.