Micronized opioid compositions, formulations and dosage forms and methods of making same

Abstract

Novel compositions, formulations and dosage forms comprising stabilized micronizedopioid particles are disclosed. Exemplary opioids include oxycodone, oxymorphone, hydrocodone, and hydromorphone, including as free bases or as salts. Stabilized micronized opioid particles having a DV 90 particle size distribution of less and or equal to 10μ or less than or equal to 20μ are disclosed. Methods for micronizing an opioid to provide stabilized micronized opioid particles are also disclosed.

1 . A composition comprising stabilized micronized opioid particles, wherein the opioid particles have a DV 90  particle size distribution of less than or equal to about 10 μm. 
     
     
         2 . The composition of  claim 1 , wherein the opioid is oxycodone, oxymorphone, hydromorphone, or hydrocodone. 
     
     
         3 . The composition of  claim 1 , wherein the opioid is in the form of a free base. 
     
     
         4 . The composition of  claim 1 , wherein the opioid is in the form of a salt. 
     
     
         5 . The composition of  claim 2 , wherein the oxycodone is oxycodone HCl. 
     
     
         6 . The composition of  claim 2 , wherein the oxycodone is oxycodone freebase. 
     
     
         7 . The composition of  claim 1 , wherein ≦1% of the stabilized micronized opioid particles have a particle size ≦0.2 μm. 
     
     
         8 . The composition of  claim 1 , wherein the opioid comprises less than 30 ppm of α,β-unsaturated ketones (ABUK). 
     
     
         9 . The composition of  claim 1 , wherein the composition comprises 5 mg of the stabilized micronized opioid particles. 
     
     
         10 . The composition of  claim 1 , wherein the composition comprises 10 mg of the stabilized micronized opioid particles. 
     
     
         11 . The composition of  claim 1 , wherein the composition comprises 20 mg of the stabilized micronized opioid particles. 
     
     
         12 . The composition of  claim 1 , wherein the composition comprises 30 mg of the stabilized micronized opioid particles. 
     
     
         13 . The composition of  claim 1 , wherein the composition comprises 40 mg of the stabilized micronized opioid particles. 
     
     
         14 . The composition of  claim 1 , wherein the composition is a non-aerosol composition. 
     
     
         15 . The composition of  claim 1 , wherein the composition is provided in a liquid suspension or a non-tablet dosage form. 
     
     
         16 . The composition of  claim 1 , wherein the composition is suitable for oral administration. 
     
     
         17 . A method for preparing micronized opioid particles comprising (a) colliding particles of a non-micronized opioid injected with an injector gas into an air jet mill in the presence of a grinding gas for a period of time and under gas pressure levels sufficient to micronize the opioid, wherein the injector gas pressure is greater than the grinding gas pressure, and wherein the micronized opioid particles have a DV90 particle size distribution of less than or equal to about 10 μm, and (b) packaging the micronized opioid particles under desiccation. 
     
     
         18 . The method of  claim 17 , wherein the opioid is oxycodone, oxymorphone, hydromorphone, or hydrocodone. 
     
     
         19 . The method of  claim 17 , wherein the opioid is in the form of a free base. 
     
     
         20 . The method of  claim 17 , wherein the opioid is in the form of a salt. 
     
     
         21 . The method of  claim 18 , wherein the oxycodone is oxycodone HCl. 
     
     
         22 . The method of  claim 18 , wherein the oxycodone is oxycodone freebase. 
     
     
         23 . The method of  claim 17 , wherein ≦1% of the micronized opioid particles have a particle size ≦0.2 μm. 
     
     
         24 . The method of  claim 17 , wherein the micronized opioid particles comprise less than 30 ppm of α,β-unsaturated ketones (ABUK).