Methods for administering aripiprazole

Abstract

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.