N-ethyl-n-phenyl-1,2-dihydro-4,5-di-hydroxy-1-methyl-2-oxo-3-quinolinecarboxamide, preparation and uses thereof

Abstract

The subject invention provides a pharmaceutical composition containing laquinimod or a pharmaceutically acceptable salt thereof, and a compound of N-ethyl-N-phenyl-1,2-dihydro-4,5-di-hydroxy-1-methyl-2-oxo-3-quinolinecarboxamide or a salt thereof.

What is claimed is: 
     
         1 - 28 . (canceled) 
     
     
         29 . A process for preparing a pharmaceutical composition comprising laquinimod or a pharmaceutically acceptable salt thereof, comprising: admixing laquinimod or a pharmaceutically acceptable salt thereof with at least one pharmaceutically acceptable carrier in a low-light environment to form the pharmaceutical composition. 
     
     
         30 . The process of  claim 29  wherein the pharmaceutical composition further comprises N-ethyl-N-phenyl-1,2-dihydro-4,5-di-hydroxy-1-methyl-2-oxo-3-quinolinecarboxamide in an amount of less than 0.5% by weight relative to the amount of laquinimod. 
     
     
         31 . The process of  claim 29  wherein the laquinimod or the pharmaceutically acceptable salt thereof is admixed with a liquid to form a solution. 
     
     
         32 . The process of  claim 31  wherein the liquid is water. 
     
     
         33 . The process of  claim 31  wherein the solution is combined with at least one solid pharmaceutical excipient to form a wet granulate. 
     
     
         34 . The process of  claim 33 , further comprising drying the wet granulate in a low-light environment. 
     
     
         35 . The process of  claim 34 , further comprising compressing the dried granulate into tablets in a low-light environment or filling the dried granulate into capsules in a low light environment. 
     
     
         36 . (canceled) 
     
     
         37 . The process of  claim 34 , wherein the low-light environment is an environment within non-transparent vessels or an environment in which only yellow fluorescent light present. 
     
     
         38 - 65 . (canceled) 
     
     
         66 . A pharmaceutical composition comprising laquinimod or a pharmaceutically acceptable salt thereof prepared by the process of  claim 29 , wherein the pharmaceutical composition comprises N-ethyl-N-phenyl-1,2-dihydro-4,5-di-hydroxy-1-methyl-2-oxo-3-quinolinecarboxamide in an amount of less than 0.5% by weight relative to the amount of laquinimod. 
     
     
         67 . The pharmaceutical composition of  claim 66 , further comprising a light-resistant coating wherein the coating is resistant to light with wavelength in the range of 310-400 nm. 
     
     
         68 . The pharmaceutical composition of  claim 67 , wherein the light-resistant coating is a coating comprising titanium dioxide. 
     
     
         69 . The pharmaceutical composition of  66  in the form of a tablet or a capsule. 
     
     
         70 . The pharmaceutical composition of  claim 66  in a light-resistant packaging. 
     
     
         71 . The pharmaceutical composition of  claim 70 , wherein the light-resistant packaging is an opaque blister pack or an opaque high density polyethylene (HPDE) container. 
     
     
         72 . The pharmaceutical composition of  claim 71 , wherein the opaque blister pack comprises:
 a) a blend of aluminum and aluminum-silver;   b) a blend of aluminum and poly-chloro-trifluoro-ethylene; or   c) a blend of two or more of polyvinyl chloride, polyethylene, polycarbonate, polyvinylidene chloride and ethylene vinyl alcohol.   
     
     
         73 . The pharmaceutical composition of  claim 71 , wherein the opaque high density polyethylene (HPDE) container is a bottle which is:
 a) an opaque high density polyethylene bottle capped with polypropylene child-resistant screw caps fitted with a silica desiccant insert; or   b) an opaque high density polyethylene bottle capped with polypropylene child-resistant screw caps with aluminum induction seal.   
     
     
         74 . The pharmaceutical composition of  claim 66 , further comprising N-ethyl-N-phenyl-1,2-dihydro-4,5-di-hydroxy-1-methyl-2-oxo-3-quinolinecarboxamide in an amount greater than about 0.02% and less than 0.50%, by weight, relative to the amount of laquinimod, based on a determination by an HPLC method. 
     
     
         75 . The pharmaceutical composition of  claim 74 , wherein the amount of N-ethyl-N-phenyl-1,2-dihydro-4,5-di-hydroxy-1-methyl-2-oxo-3-quinolinecarboxamide in the composition is greater than about 0.02% and less than about 0.10% by weight relative to the amount of laquinimod. 
     
     
         76 . The pharmaceutical composition of  claim 74 , wherein the amount of N-ethyl-N-phenyl-1,2-dihydro-4,5-di-hydroxy-1-methyl-2-oxo-3-quinolinecarboxamide is greater than about 0.05% and less than 0.50% by weight relative to the amount of laquinimod. 
     
     
         77 . The pharmaceutical composition of  claim 66 , wherein the pharmaceutically acceptable salt of laquinimod is a sodium salt.