Pharmaceutical compositions of fumaric acid esters

1. A pharmaceutical dosage form comprising:

(a) from about 1 mg to about 600 mg (N,N-diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate; and

(b) one or more compounds of Formulae (I), (II), (III), (IV), (V), (VI), (XIII), (XV):

 and

N,N-diethyl-2-hydroxyacetamide, wherein:

each of R 1 through R 4 is independently chosen from hydrogen, methyl and (N,N-diethyl carbamoyl)methyl;

each R 5 and R 7 is independently chosen from hydrogen, methyl, and (N,N-diethyl carbamoyl)methyl;

Y is chosen from O, S, NH and NR 8 ;

R 6 is chosen from hydrogen, lower alkyl, substituted lower alkyl, aryl, and substituted aryl;

R 8 is chosen from lower alkyl;

each of R 9 and R 10 is independently chosen from hydrogen, methyl, and (N,N-diethylcarbamoyl)methyl;

each of R 11 and R 12 is independently chosen from hydrogen, methyl, and (N,N-diethyl carbamoyl)methyl;

each of R 13 and R 14 is independently chosen from hydrogen, methyl, and (N,N-diethyl carbamoyl)methyl;

Q is —O—, —S—, —NH—, N(R 17 )— or —C(R 18 ) 2 —;

each of R 15 and R 16 is independently chosen from hydrogen, methyl, and (N,N-diethyl carbamoyl)methyl;

R 17 is (N,N-diethylcarbamoyl)methyl or alkyl;

each R 18 is independently hydrogen or alkyl;

each of R 37 and R 38 is independently chosen from hydrogen, methyl, and (N,N-diethylcarbamoyl)methyl;

R 41 is (N,N-diethylcarbamoyl)methyl;

R 42 is chosen from hydrogen, ethyl, and (N,N-diethylcarbamoyl)methyl;

wherein the one or more compounds of Formulae (I), (II), (III), (IV), (V), (VI), (XIII), (XV), and N,N-diethyl-2-hydroxyacetamide is present in a combined total amount of 0.001% to 3% by weight based on total weight of the (N,N-diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate, and the one or more compounds of Formula (I) is present in a combined amount total of less than 1.4% by weight based on the total weight of the (N,N-diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate; and

and the dosage form is a tablet.

2. The dosage form of claim 1 , wherein any one of the one or more compounds of Formulae (I), (II), (III), (IV), (V), (VI), (XIII), and (XV), and N,N-diethyl-2-hydroxyacetamide is present in a combined total amount of about 0.001% to about 2% by weight based on total weight of the (N,N-diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate.

3. The dosage form of claim 1 , wherein any one of the one or more compounds of Formulae (I), (II), (III), (IV), (V), (VI), (XIII), and (XV), and N,N-diethyl-2-hydroxyacetamide is present in an amount of about 0.001% to about 0.2% by weight based on total weight of the (N,N-diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate.

4. The dosage form of claim 1 , including a pharmaceutically acceptable vehicle.

5. The dosage form of claim 4 , 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 containing a compound of Formula (I), comprising an opaque layer that is free of the (N,N-diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate.

7. The dosage form of claim 1 , wherein the therapeutically effective amount of (N,N-diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate is from about 100 mg to about 1 g per day.