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 (V):
isomers thereof and salts of any of the foregoing, wherein:
each of R 13 and R 14 is independent chosen from hydrogen and methyl; and wherein the one or more compounds of Formula (V) are present in a combined total amount of about 0.0010% 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 (V) are present in a combined total amount of about 0.001% to 1% by weight based on total weight of the dimethyl fumarate.
3. The dosage form of claim 1 , wherein each of the one or more compounds of Formula (V) is present in an amount of about 0.001% to 0.3% by weight based on total weight of the dimethyl fumarate.
4. The dosage form of claim 1 , wherein each of the one or more compounds of Formula (V) is present in an amount of about 0.0010% to 0.2% weight based on total weight of the dimethyl fumarate.
5. The dosage form of claim 1 , wherein the one or more compounds of Formula (V) are selected from: 2,3-dihydroxysuccinic acid dimethyl ester, 2,3-dihydroxysuccinic acid monomethyl ester, 2,3-dihydroxysuccinic acid, isomers thereof and salts of any of the foregoing.
6. The dosage form of claim 5 , wherein the one or more compounds of Formula (V) is 2,3-dihydroxysuccinic acid dimethyl ester, isomers thereof, or salts thereof.
7. The dosage form of claim 5 , wherein the one or more compounds of Formula (V) is 2,3-dihydroxysuccinic acid monomethyl ester, isomers thereof, or salts thereof.
8. The dosage form of claim 5 , wherein the one or more compounds of Formula (V) is 2,3-dihydroxysuccinic acid, isomers thereof, or salts thereof.
9. The dosage form of claim 1 , in the form of a tablet or capsule.
10. 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.
11. The dosage form of claim 1 , wherein the dosage form is substantially free of PVP, PEG and polysorbate surfactant.
12. The dosage form of claim 1 , further comprising a free radical scavenger.