Morphine Sulfate Methanolic Solvate, Processes for Making Same and Related Compositions and Methods for Treating Pain

Abstract

Processes for reducing the amount of impurities, especially α,β-unsaturated ketones (ABUK), in materials containing morphine. Novel compounds, namely low ABUK morphine sulfate methanolic solvate, and a novel crystal form are also described. The method for making morphine sulfate methanolic solvate comprises mixing a morphine free base composition with methanol to form a solution and adding a liquid comprising sulfuric acid to the solution to form a morphine sulfate methanolic solvate precipitate. A method of making a morphine sulfate compound comprises drying the morphine sulfate methanolic solvate in the presence of water vapor, such that methanol molecules are removed and replaced with water vapor molecules. A composition for treating pain comprises the morphine sulfate compound and at least one pharmaceutically acceptable excipient. A method for treating pain comprises administering to a patient in need thereof the composition comprising the morphine sulfate compound and at least one pharmaceutically acceptable excipient.

What is claimed is: 
     
         1 . A composition comprising crystalline morphine sulfate solvate and less than 25 ppm morphinone. 
     
     
         2 . A composition comprising >98.9 area percent morphine base as determined by liquid chromatography. 
     
     
         3 . The composition of  claim 2 , having >99.6 area percent morphine base. 
     
     
         4 . The composition of  claim 2 , further comprising <0.5 area percent codeine. 
     
     
         5 . The composition of  claim 4 , having <0.06 area percent codeine. 
     
     
         6 . The composition of  claim 2 , further comprising <3.3% water as determined by Karl Fischer analysis. 
     
     
         7 . The composition of  claim 6 , having <0.3% water. 
     
     
         8 . The composition of  claim 2 , further comprising <65 ppm morphinone. 
     
     
         9 . The composition of  claim 8 , having <25 ppm morphinone. 
     
     
         10 . A composition comprising morphine sulfate and <125 ppm morphinone. 
     
     
         11 . The composition of  claim 10 , further comprising <0.11% ethanol as determined by gas chromatography. 
     
     
         12 . The composition of  claim 10 , further comprising <10% water by Karl Fischer analysis. 
     
     
         13 . A method of making a composition comprising the steps of:
 a. mixing concentrated poppy straw and an alcohol;   b. heating the mixture to dissolve the concentrated poppy straw;   c. adding water to the mixture;   d. cooling the mixture to precipitate the composition from the mixture; and   e. filtering the composition,
 wherein the composition comprises ≧98.9 area percent morphine base as determined by liquid chromatography. 
   
     
     
         14 . The method of  claim 13 , further comprising the steps of:
 a. mixing the composition with an alcohol;   b. heating the mixture to dissolve the composition;   c. adding water to the mixture;   d. cooling the mixture to precipitate a solid from the mixture; and   e. filtering the solid
 wherein the solid comprises ≧99.6 area percent morphine base as determined by liquid chromatography. 
   
     
     
         15 . The method of  claim 14 , wherein the solid is crystalline.