ORAL PHARMACEUTICAL COMPOSITION OF METHYLERGONOVINE
An oral modified release pharmaceutical composition of methylergonovine suitable for oral once daily administration is provided. The composition includes at least about 0.6 mg dose of methylergonovine or a pharmaceutically acceptable salt thereof and is particularly useful for treating migraine or refractory migraine.
1 . An oral modified release pharmaceutical composition configured for once daily administration comprising at least about 0.6 mg methylergonovine or a pharmaceutically acceptable salt thereof.
2 . The modified release composition of claim 1 , wherein said composition provides release of methylergonovine or a pharmaceutically acceptable salt thereof over a period ranging from more than 0 hours to up to 24 hours.
3 . The modified release composition of claim 1 , wherein said composition provides extended release of methylergonovine or a pharmaceutically acceptable salt thereof, with or without an initial load dose.
4 . The modified release composition of claim 3 , wherein said composition comprise:
(a) at least one extended release portion comprising methylergonovine or a pharmaceutically acceptable salt thereof, and
(b) optionally, at least one immediate release portion comprising methylergonovine or a pharmaceutically acceptable salt thereof.
5 . The modified release composition of claim 4 , wherein the extended release portion exhibits release of methylergonovine or a pharmaceutically acceptable salt thereof over a period of up to 24 hours after oral administration.
6 . The modified release composition of claim 4 , wherein the extended release portion comprises at least about 0.4 mg to about 1.6 mg methylergonovine or a pharmaceutically acceptable salt thereof.
7 . The modified release composition of claim 4 , wherein said immediate release portion comprises at least about 0.2 mg to about 0.6 mg methylergonovine or a pharmaceutically acceptable salt thereof.
8 . The modified release composition of claim 1 , wherein said composition is a solid oral dosage form selected from a tablet, a multilayer tablet, a capsule, a caplet, granules, pellets, powder, and granules, pellets or powder filled in a capsule.
9 . The modified release composition of claim 1 , wherein the pharmaceutically acceptable salt of methylergonovine is maleate.
10 . The modified release composition of claim 1 , wherein the pharmaceutically acceptable salt of methylergonovine is tartrate.
11 . A modified release oral composition configured for once daily administration comprising:
(a) a core comprising at least about 0.4 mg to about 1.6 mg methylergonovine or a pharmaceutically acceptable salt thereof exhibiting extended release, and
(b) at least one layer surrounding the core comprising at least about 0.2 mg to about 0.6 mg methylergonovine or a pharmaceutically acceptable salt thereof exhibiting immediate release.
12 . A solid oral unit dosage form configured for once daily administration comprising:
(a) at least one layer comprising least about 0.2 mg to about 0.6 mg methylergonovine or a pharmaceutically acceptable salt thereof exhibiting immediate release, and
(b) at least one layer comprising about 0.4 mg to about 1.6 mg methylergonovine or a pharmaceutically acceptable salt thereof exhibiting extended release.
13 . A method for the treatment of a methylergonovine responsive condition selected from migraine, refractory migraine, uterine atony, uterine haemorrhage, subinvolution of the uterus, or uterine haemorrhage in the second stage of labor, said method comprising once daily oral administration of the modified release composition of claim 1 .
14 . The method of claim 16 , wherein said methylergonovine responsive condition is refractory migraine.