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, wherein said dimethyl fumarate is the only drug in the dosage form; and
(b) one or more compounds of Formula (I):
isomers thereof and salts of any of the foregoing, wherein:
each of R 1 through R 4 is independently chosen from hydrogen and methyl wherein at least one of R 1 -R 4 is hydrogen; and wherein the one or more compounds of Formula (I) are impurities and are present in the dosage form in a combined total amount of 0.001% to 2% by weight based on total weight of the dimethyl fumarate; and
(c) a pharmaceutically acceptable vehicle.
2. The dosage form of claim 1 , wherein the one or more compounds of Formula (I) are present in a combined total amount of 0.001% to less than 1% 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 (I) are selected from 3,4-bis(methoxycarbonyl)cyclobutane-1,2-dicarboxylic acid, 2,4-bis(methoxycarbonyl)cyclobutane-1,3-dicarboxylic acid, cyclobutane-1,2,3,4-tetracarboxylic acid, and isomers thereof and salts of any of the foregoing.
4. The dosage form of claim 1 , wherein the one or more compounds of Formula I are 1R, 2R, 3S, 4S-isomers.
5. The dosage form of claim 3 , wherein each of the one or more compounds of Formula (I) is in an amount of 0.001% to 0.3% by weight based on total weight of the dimethyl fumarate.
6. The dosage form of claim 3 , wherein each of the one or more compounds of Formula (I) is in an amount of 0.001% to 0.2% by weight based on total weight of the dimethyl fumarate.
7. 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.
8. The dosage form of claim 1 , wherein the opaque coating is free of dimethyl fumarate.
9. The dosage form of claim 1 , wherein the dosage form is enclosed in a package that limits exposure of the dosage form to ambient light.
10. The dosage form of claim 9 , wherein the package is a bottle comprising an opaque polymer.
11. The dosage form of claim 9 , wherein the package is a blister pack comprising metal foil.
12. The dosage form of claim 11 , wherein the blister pack comprises an opaque polymer.
13. The dosage form of claim 1 wherein the dosage form is in the form of a tablet or capsule having an opaque coating comprising a compound selected from the group consisting of iron oxide, a colorant, titanium dioxide, zinc oxide and combinations thereof and the dosage form does not contain polyvinylpyrrolidine.