CONTROLLED RELEASE PHARMACEUTICAL COMPOSITIONS COMPRISING A FUMARIC ACID ESTER
The invention features a delayed release composition wherein the active ingredient consists essentially of about 240 mg of dimethylfumarate and one or more pharmaceutically acceptable excipients.
1 . A delayed release composition wherein the active ingredient consists essentially of about 240 mg of dimethylfumarate and one or more pharmaceutically acceptable excipients.
2 . The composition of claim 1 , wherein the composition contains a methacrylic acid copolymer.
3 . The composition of claim 1 , wherein the pharmaceutically acceptable excipients comprise one or more of the following excipients micro crystalline cellulose, cross-linked sodium carboxymethylcellulose, talc, silica, colloidal silicon dioxide, magnesium stearate, or a surfactant having an HLB value above 8.
4 . The composition of claim 3 , wherein the composition comprises from about 1 to about 60% micro crystalline cellulose.
5 . The composition of claim 3 , wherein the composition comprises from about 0.2 to about 3% magnesium stearate.
6 . The composition of claim 3 , wherein the composition comprises from about 0.2 to about 4% silica.
7 . The composition of claim 3 , wherein the composition comprises cross-linked sodium carboxymethylcellulose.
8 . The composition of claim 3 , wherein the composition comprises a surfactant having an HLB value above 8.
9 . The composition of claim 1 , wherein the dimethylfumarate is in the form of micro crystals.
10 . The composition of claim 9 , wherein the composition comprises micro crystals between 315 and 710 microns.
11 . The composition of claim 1 , wherein following oral administration of the unit dosage form to a human subject monomethylfumarate appears in the plasma of the subject with a Cmax of about 2 mg/L.
12 . The composition of claim 11 , wherein the time period for the plasma concentration to decrease to reach 50% of the Cmax is at least 2 hours.
13 . The composition of claim 12 , wherein the time period for the plasma concentration to decrease to reach 50% of the Cmax is in a range of from about 2 to about 15 hours.
14 . The composition of claim 13 , wherein the time period for the plasma concentration to decrease to reach 50% of the Cmax is in a range of from about 2 to about 10 hours.
15 . The composition of claim 14 , wherein the time period for the plasma concentration to decrease to reach 50% of the Cmax is in a range of from about 3 to about 8 hours.
16 . The composition of claim 1 , wherein the composition is a unit dosage form that is a capsule or a tablet.
17 . The composition of claim 16 , wherein the capsule is a hard gelatin capsule.
18 . The composition of claim 1 , wherein the composition is a unit dosage form comprising microtablets.
19 . The composition of claim 18 , wherein the microtablets have an enteric coating.
20 . The composition of claim 1 , wherein the composition is a unit dosage form comprising beads.
21 . The composition of claim 1 , wherein said dimethylfumarate is in the form of micro crystals.
22 . The composition of claim 21 , wherein the composition is a capsule containing enteric coated micro crystals that have one coating layer.
23 . The composition of claim 21 , wherein the capsule comprises micro crystals between 315 and 710 microns.
24 . A method of treating a subject by administering a delayed release composition of claim 1 , wherein 240 mg of said composition is administered twice daily.
25 . The method of claim 24 , wherein about 240 mg is administered in the morning and the remainder is administered later in the day.
26 . The composition of claim 2 , wherein the methacrylic acid is in a layer.
27 . The composition of claim 26 , wherein the composition contains one layer.
28 . The composition of claim 1 , wherein the composition is a unit dosage form comprising pellets.
29 . The composition of claim 28 , wherein the methacrylic acid is in a layer on the pellets.