ORAL PHARMACEUTICAL COMPOSITION OF METHYLERGONOVINE AND METHODS OF USE THEREOF
A solid pharmaceutical oral composition for twice daily administration is provided. The composition includes from about 0.3 mg to about 0.6 mg in total of methylergonovine or a pharmaceutically acceptable salt thereof. The composition is used for treating a subject having a methylergonovine responsive condition such as migraine, refractory migraine, uterine atony, uterine haemorrhage, subinvolution of the uterus, and uterine haemorrhage in the second stage of labor.
1 . A solid pharmaceutical oral composition configured for twice daily administration, comprising from about 0.3 mg to about 0.6 mg in total of methylergonovine or a pharmaceutically acceptable salt thereof.
2 . The solid pharmaceutical oral composition of claim 1 , wherein the solid pharmaceutical oral composition comprises about 0.4 mg in total of methylergonovine or a pharmaceutically acceptable salt thereof.
3 . The solid pharmaceutical oral composition of claim 1 , wherein the solid pharmaceutical oral composition comprises an extended release matrix comprising methylergonovine or a pharmaceutically acceptable salt thereof.
4 . The solid pharmaceutical oral composition of claim 3 , wherein the extended release matrix comprises a hydrophilic release rate controlling compound, a hydrophobic release rate controlling compound, or a combination thereof.
5 . The solid pharmaceutical oral composition of claim 4 , wherein the extended release matrix comprises methylergonovine or a pharmaceutically acceptable salt thereof, the hydrophilic release rate controlling compound, the hydrophobic release rate controlling compound or both in an intragranular portion, an extragranular portion or both.
6 . The solid pharmaceutical oral composition of claim 3 , wherein the extended release matrix comprises
an intragranular portion comprising methylergonovine or a pharmaceutically acceptable salt thereof, and at least one excipient, and
an extragranular portion comprising at least one release rate controlling compound.
7 . The solid pharmaceutical oral composition of claim 3 , further comprising an immediate release layer comprising methylergonovine or a pharmaceutically acceptable salt thereof, the immediate release layer at least partially disposed on the extended release matrix, wherein the solid pharmaceutical oral composition has a bilayer structure.
8 . The solid pharmaceutical oral composition of claim 7 , wherein the immediate release layer comprises at about 0.1 mg of methylergonovine or a pharmaceutically acceptable salt thereof.
9 . The solid pharmaceutical oral composition of claim 3 , further comprising an immediate release overcoat comprising methylergonovine or a pharmaceutically acceptable salt thereof, the immediate release overcoat disposed on and covering the extended release matrix.
10 . The solid pharmaceutical oral composition of claim 9 , wherein the immediate release overcoat comprises about 0.1 mg of methylergonovine or a pharmaceutically acceptable salt thereof.
11 . The solid pharmaceutical oral composition of claim 3 , further comprising
an extended release coat comprising a hydrophilic release rate controlling compound and/or a hydrophobic release rate controlling compound, the extended release coat disposed on and covering the extended release matrix, and
an immediate release overcoat comprising methylergonovine or a pharmaceutically acceptable salt thereof, the immediate release overcoat disposed on and covering the extended release coat.
12 . The solid pharmaceutical oral composition of claim 11 , wherein the immediate release overcoat comprises about 0.1 mg of methylergonovine or a pharmaceutically acceptable salt thereof.
13 . The solid pharmaceutical oral composition of claim 1 , wherein the solid pharmaceutical oral composition in a form selected from a tablet; a capsule; granules; pellets; powder; or granules, pellets, powder or a combination thereof filled in a capsule.
14 . The solid pharmaceutical oral composition of claim 1 , wherein the pharmaceutically acceptable salt of methylergonovine is maleate.
15 . The solid pharmaceutical oral composition of claim 1 , wherein the solid pharmaceutical oral composition is configured to provide a dissolution profile of a release of methylergonovine or a pharmaceutically acceptable salt thereof
within 0.5 hours being between about 10% and about 35%,
within 3 hours being between about 30% and about 60%,
within 6 hours being between about 40% and about 85%, and
within 10 hours being not less than 70%,
as measured by a dissolution method employing a USP Type-II dissolution apparatus equipped with a paddle, a rotation speed of 75 rpm and 900 mL of tartaric acid (1 in 200 w/w) as dissolution medium.
16 . A method for treating a subject having a methylergonovine responsive condition comprising a step of administering to the subject in need thereof a therapeutic effective amount of the solid pharmaceutical oral composition of claim 1 .
17 . The method for treating a subject having a methylergonovine responsive condition of claim 16 , wherein the methylergonovine responsive condition is selected from migraine, refractory migraine, uterine atony, uterine haemorrhage, subinvolution of the uterus, or uterine haemorrhage in the second stage of labor.
18 . The method for treating a subject having a methylergonovine responsive condition of claim 16 , wherein the subject is a human.