FORMULATIONS PHARMACOKINETICS OF DEUTERATED BENZOQUINOLINE INHIBITORS OF VESICULAR MONOAMINE TRANSPORTER 2
The present invention relates to new pharmaceutical compositions comprising benzoquinoline compounds, and methods to inhibit vesicular monoamine transporter 2 (VMAT2) activity in a subject for the treatment of chronic hyperkinetic movement disorders.
1 . A solid deutetrabenazine oral dosage form comprising deutetrabenazine and a poly(ethylene oxide) polymer.
2 . The oral dosage form according to claim 1 in the form of a tablet comprising a tablet core and a coating, wherein the deutetrabenazine and poly(ethylene oxide) polymer are in the tablet core.
3 . The oral dosage form according to claim 1 that releases the deutetrabenazine over a period of up to about 4 hours.
4 . The oral dosage form according to claim 1 that releases the deutetrabenazine over a period of up to about 8 hours.
5 . The oral dosage form according to claim 1 wherein the poly(ethylene oxide) polymer is POLYOX® N60K.
6 . The oral dosage form according to claim 1 comprising about 5-20% by weight of the poly(ethylene oxide) polymer.
7 . The oral dosage form according to claim 1 comprising about 1-15% by weight of deutetrabenazine.
8 . The oral dosage form according to claim 1 further comprising one or more of a filler, a lubricant, a binder, an absorbent, an antioxidant, a solubilizing agent, a dispersant, and a colorant.
9 . The oral dosage form according to claim 1 comprising about 1-15% by weight of deutetrabenazine and about 5-20% by weight of the poly(ethylene oxide) polymer, and further comprising:
about 60-70% by weight of a filler;
about 15-25% by weight of an absorbent;
about 1-10% by weight of a dispersant;
about 0.5-2% by weight of a solubilizing agent; and,
about 0.5-2% by weight of a lubricant.
10 . The oral dosage form according to claim 9 further comprising about 0.1-0.2% by weight of an antioxidant.
11 . The oral dosage form according to claim 10 , wherein the antioxidant is one or both of butylated hydroxyanisole and butylated hydroxytoluene.
12 . The oral dosage form according to claim 11 comprising about 1-15% by weight of deutetrabenazine;
about 5-20% by weight of a poly(ethylene oxide) polymer,
about 60-70% by weight of mannitol;
about 15-25% by weight of microcrystalline cellulose;
about 1-10% by weight of a polyvinylpyrrolidone;
about 0.5-2% by weight of a polysorbate;
about 0.5-2% by weight of magnesium stearate; and,
about 0.1-0.2% by weight of one or both of butylated hydroxyanisole and butylated hydroxytoluene.