Pharmaceutical compositions of dimethyl fumarate
Pharmaceutical compositions and dosage forms of dimethyl fumarate containing low levels of certain impurities are disclosed.
1. A dosage form for treating multiple sclerosis, comprising:
(a) a therapeutically effective amount of dimethyl fumarate in solid form;
(b) one or more compounds of Formula (II):
isomers thereof and salts of any of the foregoing, wherein:
each of R 5 and R 7 is independently chosen from hydrogen and methyl;
Y is chosen from O, S, NH and NR 8 ;
R 6 is chosen from hydrogen, lower alkyl and aryl;
R 8 is chosen from lower alkyl; and
wherein the one or more compounds of Formula (II) are present in a combined total amount of 0.001% to 3% by weight based on total weight of dimethyl fumarate; and
(c) a pharmaceutically acceptable vehicle.
2. The dosage form of claim 1 , wherein the one or more compounds of Formula (II) are present in a combined total amount of 0.001% to 2% by weight based on total weight of the dimethyl fumarate.
3. The dosage form of claim 1 , wherein the one or more compounds of Formula (II) are present in a combined total amount of 0.001% to 1% by weight based on total weight of the dimethyl fumarate.
4. The dosage form of claim 1 , wherein the one or more compounds of Formula (II) are selected from dimethyl-2-hydroxysuccinate; 2-hydroxy-4-methoxy-4-oxobutanoic acid; 3-hydroxy-4-methoxy-4-oxobutanoic acid; 2-hydroxysuccinic acid; dimethyl 2-mercaptosuccinate; 2-mercapto-4-methoxy-4-oxobutanoic acid; 3-mercapto-4-methoxy-4-oxobutanoic acid; 2-mercaptosuccinic acid; dimethyl 2-aminosuccinate; 2-amino-4-methoxy-4-oxobutanoic acid; 3-amino-4-methoxy-4-oxobutanoic acid; 2-aminosuccinic acid; isomers thereof and salts of any of the foregoing.
5. The dosage form of claim 1 , wherein the pharmaceutically acceptable vehicle is selected from a carrier, a diluent, an excipient, a wetting agent, an emulsifier, a buffer, a stabilizer, a thickener, a lubricant, a coloring agent and combinations thereof.
6. The dosage form of claim 1 , in the form of a tablet or capsule.
7. The dosage form of claim 1 , wherein the dosage form is substantially free of compounds capable of acting as a nucleophile for addition to the double bond of DMF.