Pharmaceutical compositions of dimethyl fumarate

Abstract

The present invention relates to pharmaceutical compositions comprising dimethyl fumarate and a pharmaceutically acceptable agent which inhibits the enzyme catalyzed degradation of dimethyl fumarate.

1 . An oral pharmaceutical composition comprising a core comprising dimethyl fumarate and a pharmaceutically acceptable agent that inhibits the enzyme catalyzed degradation of dimethyl fumarate, and an enteric coating,
 wherein the oral pharmaceutical composition does not release dimethyl fumarate in acidic fluids in a stomach but once the composition is emptied from the stomach into an intestine the enteric coating dissolves and the dimethyl fumarate and the pharmaceutically acceptable agent are released,   said oral pharmaceutical composition provides an increased bioavailability in humans such that the dose of dimethyl fumarate is reduced by about 10% to about 20% when compared to an oral pharmaceutical composition devoid of the pharmaceutically acceptable agent that inhibits the enzyme catalyzed degradation of dimethyl fumarate.   
     
     
         2 . The oral pharmaceutical composition of  claim 1 , wherein the composition further comprises an alkalizer. 
     
     
         3 . The oral pharmaceutical composition of  claim 1 , wherein the pharmaceutically acceptable agent is aspartame. 
     
     
         4 . The oral pharmaceutical composition of  claim 3 , wherein an amount of aspartame is in a range of about 10% to about 15% based on a weight of dimethyl fumarate. 
     
     
         5 . The oral pharmaceutical composition of  claim 1 , wherein the oral pharmaceutical composition is in the form of a capsule comprising minitablets. 
     
     
         6 . The oral pharmaceutical composition of  claim 5 , wherein the oral pharmaceutical composition comprises dimethyl fumarate in an amount from 195 to 215 mg/capsule. 
     
     
         7 . The oral pharmaceutical composition of  claim 5 , wherein the oral pharmaceutical composition comprises dimethyl fumarate in an amount from 4.3 to 8.6 mg/minitablet. 
     
     
         8 . The oral pharmaceutical composition of  claim 6 , wherein the oral pharmaceutical composition comprises 204 mg of dimethyl fumarate. 
     
     
         9 . A method of increasing bioavailability of dimethyl fumarate, the method comprising orally administering a pharmaceutical composition comprising a core and a delayed release coating, said core comprising dimethyl fumarate and a pharmaceutically acceptable agent that inhibits enzyme catalyzed degradation of dimethyl fumarate. 
     
     
         10 . The method of  claim 9 , wherein the pharmaceutical composition further comprises an alkalizer. 
     
     
         11 . The method of  claim 9 , wherein the pharmaceutically acceptable agent is aspartame. 
     
     
         12 . The method of  claim 11 , wherein the amount of aspartame is in a range of about 10% to about 15% of a weight of dimethyl fumarate. 
     
     
         13 . The method of  claim 9 , wherein the oral pharmaceutical composition is in the form of a capsule comprising minitablets. 
     
     
         14 . The method of  claim 13  wherein the composition comprises dimethyl fumarate in an amount from 195 mg to 215 mg/capsule. 
     
     
         15 . The method of  claim 13 , wherein the composition comprises dimethyl fumarate in an amount from 4.3 to 8.6 mg/minitablet. 
     
     
         16 . The method as in  claim 14 , wherein the composition comprises 204 mg of dimethyl fumarate. 
     
     
         17 . A method of therapy comprising administering the oral pharmaceutical composition of  claim 1  to a patient in need thereof. 
     
     
         18 . A method of increasing the bioavailability of dimethyl fumarate comprising administering the oral pharmaceutical composition of  claim 1  to a patient in need thereof. 
     
     
         19 . A method of treating one or more conditions selected from the group consisting of multiple sclerosis, psoriasis, psoriatic arthritis, neurodermatitis, inflammatory bowel disease, such as Crohn's disease and ulcerative colitis, polyarthritis, rheumatoid arthritis, lupus nephritis and myasthenia gravis comprising administering the oral pharmaceutical composition of  claim 1  to a patient in need thereof. 
     
     
         20 . A method of preventing or reducing the risk of organ transplantation rejection comprising administering the oral pharmaceutical composition of  claim 1  to a patient in need thereof.