Methods for administering aripiprazole
The present invention relates, in part, to the discovery that a pharmaceutical composition comprising aripiprazole and a carrier administered in a bolus injection resulted in an extended release profile similar to that obtained by the injection of a poly lactide-co-glycolide microsphere formulation containing the active agent. This surprising result suggests that pharmacologically beneficial extended release formulations without the complexities and expense associated with the manufacture microspheres.
1 . An injectable composition for the extended release of aripiprazole comprising a mixture of at least about 10 mg/ml aripiprazole in an injection vehicle comprising An optional viscosity enhancing agent.
2 . The composition of claim 1 wherein the aripiprazole release is for at least 7 days.
3 . The composition of claim 2 wherein the viscosity enhancing agent comprises carboxymethyl cellulose.
4 . The composition of claim 3 , wherein said injection vehicle comprises at least about 1% by volume sodium carboxymethyl cellulose.
5 . The composition of claim 4 , wherein said injection vehicle comprises about 3% by volume carboxymethyl cellulose.
6 . The composition of claim 2 wherein the injection vehicle further comprises a wetting agent.
7 . The composition of claim 6 wherein the surfactant is selected from the group consisting of polysorbate 20, polysorbate 40, and polysorbate 80.
8 . The composition of claim 7 wherein the wetting agent is polysorbate 20.
9 . The composition of claim 8 wherein the injection vehicle comprises about 0.1% by weight of polysorbate 20.
10 . The composition of claim 2 , wherein said injection vehicle comprises a density enhancing agent.
11 . The composition of claim 10 , wherein said density enhancing agent comprises sorbitol.
12 . The composition of claim 2 , wherein said injection vehicle comprises a tonicity adjusting agent.
13 . The composition of claim 12 , wherein said tonicity adjusting agent comprises sodium chloride.
14 . The composition of claim 1 , wherein said injection vehicle comprises about 1% by weight of sodium chloride.
15 . A composition comprising at least about 10 mg of aripiprazole and an aqueous injection vehicle comprising water, a viscosity enhancing agent, a wetting agent and a tonicity agent.
16 . A composition comprising at least about 10 mg of aripiprazole and an aqueous injection vehicle comprising water, about 3% by volume carboxymethylcellulose, about 0.1% polysorbate 20 and about 1% by weight sodium chloride.
17 . A composition comprising at least about 10 mg of aripiprazole and an aqueous injection vehicle consisting essentially of water, about 3% by volume carboxymethylcellulose, about 0.1% by weight polysorbate 20 and about 0.9% by weight sodium chloride.
18 . A method for providing aripiprazole to an individual in an extended release injectable composition comprising administering a mixture of at least about 10 mg/ml aripiprazole in an injection vehicle comprising an optional viscosity enhancing agent.
19 . The method of claim 18 wherein the aripiprazole is present in an amount of at least about 20 mg/ml.
20 . The method of claim 19 wherein a therapeutically effective amount of the aripiprazole is present in the plasma of the individual for at least about 7 days.
21 . The method of claim 19 wherein a therapeutically effective amount of the aripiprazole is present in the plasma of the individual for at least about 14 days.
22 . The method of claim 19 wherein a therapeutically effective amount of the aripiprazole is present in the plasma of the individual for at least about 21 days.
23 . The method of claim 19 wherein the viscosity enhancing agent comprises carboxymethyl cellulose.
24 . The method of claim 23 , wherein said injection vehicle comprises at least about 1% by volume sodium carboxymethyl cellulose.
25 . The method of claim 24 , wherein said injection vehicle comprises about 3% by volume carboxymethyl cellulose.
26 . The method of claim 25 wherein the injection vehicle further comprises a wetting agent.
27 . The method of claim 26 wherein the surfactant is selected from the group consisting of polysorbate 20, polysorbate 40, and polysorbate 80.
28 . The method of claim 27 wherein the wetting agent is polysorbate 20.
29 . The method of claim 28 wherein the injection vehicle comprises about 0.1% by weight of polysorbate 20.
30 . The method of claim 22 , wherein said injection vehicle comprises a density enhancing agent.
31 . The method of claim 30 , wherein said density enhancing agent comprises sorbitol.
32 . The method of claim 22 , wherein said injection vehicle comprises a tonicity adjusting agent.
33 . The method of claim 32 , wherein said tonicity adjusting agent comprises sodium chloride.
34 . The method of claim 21 , wherein said injection vehicle comprises about 1% by weight of sodium chloride.
35 . The method of claim 18 wherein the composition is administered by injection.
36 . The method of claim 18 wherein the composition is administered intramuscularly or subcutaneously.
37 . The method of claim 18 further comprising a second administration of the composition at least about 7 days after the first administration.
38 . The method of claim 18 further comprising a second administration of the composition at least about 14 days after the first administration.