CONTROLLED RELEASE PHARMACEUTICAL COMPOSITIONS COMPRISING A FUMARIC ACID ESTER
The invention relates to a method of treating a subject in need of treatment for multiple sclerosis including orally administering to the subject in need thereof a delayed release pharmaceutical composition using an increasing dose regimen, wherein an initial daily amount of drug administered is increased later to a higher daily amount and the pharmaceutical composition consists essentially of (a) dimethylfumarate and (b) one or more pharmaceutically acceptable excipients.
1 . A method of treating a subject in need of treatment for multiple sclerosis comprising orally administering to the subject in need thereof a delayed release pharmaceutical composition using an increasing dose regimen, wherein an initial daily amount of drug administered is increased later to a higher daily amount and the pharmaceutical composition consists essentially of (a) dimethylfumarate and (b) one or more pharmaceutically acceptable excipients.
2 . The method of claim 1 , wherein the delayed release pharmaceutical composition is contained in a capsule.
3 . The method of claim 1 , wherein the delayed release pharmaceutical composition is in the form of a tablet.
4 . The method of claim 1 , wherein the delayed release pharmaceutical composition is taken with a meal.
5 . The method of claim 1 , wherein the increasing dose regimen comprises orally administering to the subject about 480 mg of dimethylfumarate a day within the regimen.
6 . The method of claim 1 , wherein the increasing dose regimen comprises (i) orally administering to the subject in need thereof the pharmaceutical composition an initial dose per day for a period of time and (ii) following step (i), orally administering to the subject in need thereof the pharmaceutical composition at a higher daily dose, wherein the higher daily dose is about twice the initial daily dose.
7 . The method of claim 6 , wherein the period of time is a week.
8 . The method of claim 7 , wherein the initial daily dose is about 240 mg per day.
9 . The method of claim 6 , wherein the pharmaceutical composition is taken with a meal.
10 . The method of claim 6 , wherein the pharmaceutical composition is contained in a capsule.
11 . The method of claim 6 , wherein the pharmaceutical composition is in the form of a tablet.
12 . The method of claim 6 , wherein the pharmaceutical composition comprises microtablets.
13 . The method of claim 12 , wherein the microtablets have an enteric coating.
14 . The method of claim 6 , wherein the pharmaceutical composition comprises pellets.
15 . The method of claim 6 , wherein the increasing dose regimen comprises orally administering to the subject about 480 mg of dimethylfumarate a day within the regimen.
16 . The method of claim 1 , wherein the pharmaceutically acceptable excipients comprise one or more of any one of the following: micro crystalline cellulose, cross-linked sodium carboxymethylcellulose, talc, silica, colloidal silicon dioxide, magnesium stearate, or a surfactant having an HLB value above 8.
17 . The method of claim 16 , wherein the dosage form comprises from about 1 to about 60% micro crystalline cellulose.
18 . The method of claim 16 , wherein the dosage form comprises from about 0.2 to about 3% magnesium stearate.
19 . The method of claim 16 , wherein the dosage form comprises from about 0.2 to about 4% silica.
20 . The method of claim 16 , wherein the dosage form comprises cross-linked sodium carboxymethylcellulose.
21 . The method of claim 16 , wherein the dosage form comprises a surfactant having an HLB value above 8.
22 . The method of claim 1 , wherein the dimethylfumarate is in the form of micro crystals.
23 . The method of claim 22 , wherein the pharmaceutical composition containing the dimethylfumarate is a capsule comprising enteric coated micro crystals that have one coating layer.
24 . The method of claim 22 , wherein the micro crystals are between 315 and 710 microns.
25 . The method of claim 15 , wherein about 240 mg dimethylfumarate is administered in the morning and the remainder is administered later in the day.
26 . The method of claim 25 , wherein said about 480 mg in a day is administered in two equal doses at different times of the day.
27 . The method of claim 1 , wherein said dimethylfumarate is administered at least 30 minutes to about two hours after a meal.
28 . The method of claim 15 , wherein said dimethylfumarate is administered at least 30 minutes to about two hours after a meal.
29 . The method of claim 6 , wherein the pharmaceutical composition comprises beads.
30 . The method of claim 29 , wherein the pharmaceutical composition comprises beads in a capsule.