Controlled release sterile injectable aripiprazole formulation and method

Abstract

A controlled release sterile freeze-dried aripiprazole formulation is provided which is formed of aripiprazole of a desired mean particle size and a vehicle therefor, which upon constitution with water and intramuscular injection releases aripiprazole over a period of at least about one week and up to about eight weeks. A method for preparing the controlled release freeze-dried aripiprazole formulation, and a method for treating schizophrenia employing the above formulation are also provided.

1 . An injectable composition for the extended release of aripiprazole comprising a suspension of at least about 10 mg/ml aripiprazole in an injection vehicle. 
     
     
         2 . The composition of  claim 1 , wherein the aripiprazole release is for at least 7 days. 
     
     
         3 . The composition of  claim 2 , wherein said injection vehicle comprises carboxymethyl cellulose. 
     
     
         4 . The composition of  claim 3 , wherein said injection vehicle comprises sodium carboxymethyl cellulose. 
     
     
         5 . The composition of  claim 4 , wherein said injection vehicle comprises about 1% by volume sodium carboxymethyl cellulose. 
     
     
         6 . The composition of  claim 2 , wherein the injection vehicle further comprises a surfactant. 
     
     
         7 . The composition of  claim 6 , wherein the surfactant is selected from the group consisting of polysorbate 20, and polysorbate 80. 
     
     
         8 . The composition of  claim 7 , wherein the surfactant is polysorbate 20. 
     
     
         9 . The composition of  claim 2 , wherein said injection vehicle comprises a bulking agent. 
     
     
         10 . The composition of  claim 9 , wherein said bulking agent comprises sorbitol. 
     
     
         11 . The composition of  claim 2 , wherein said injection vehicle comprises a member selected from the group consisting of mannitol, sucrose, glucose and sorbital. 
     
     
         12 . A composition comprising a suspension of at least about 10 mg of aripiprazole and an aqueous injection vehicle comprising water, a suspending agent, a surfactant and a bulking agent. 
     
     
         13 . A composition comprising a suspension of at least about 10 mg of aripiprazole and an aqueous injection vehicle comprising water, carboxymethylcellulose, and polysorbate 20. 
     
     
         14 . A composition comprising a suspension of at least about 10 mg of aripiprazole and an aqueous injection vehicle consisting essentially of water, carboxymethylcellulose, and polysorbate 20. 
     
     
         15 . A method for providing aripiprazole to an individual in an extended release injectable composition comprising administering the composition of  claim 1 . 
     
     
         16 . The method of  claim 15 , wherein a therapeutically effective amount of the aripiprazole is present in the plasma of the individual for at least about 7 days. 
     
     
         17 . The method of  claim 15 , wherein a therapeutically effective amount of the aripiprazole is present in the plasma of the individual for at least about 14 days. 
     
     
         18 . The method of  claim 15 , wherein a therapeutically effective amount of the aripiprazole is present in the plasma of the individual for at least about 21 days. 
     
     
         19 . The method of  claim 15 , wherein the suspending agent comprises carboxymethyl cellulose. 
     
     
         20 . The method of  claim 19 , wherein said injection vehicle comprises sodium carboxymethyl cellulose. 
     
     
         21 . The method of  claim 20 , wherein said injection vehicle comprises about 1% by volume sodium carboxymethyl cellulose. 
     
     
         22 . The method of  claim 21 , wherein the injection vehicle further comprises a surfactant. 
     
     
         23 . The method of  claim 22 , wherein the surfactant is selected from the group consisting of polysorbate 20, and polysorbate 80. 
     
     
         24 . The method of  claim 23 , wherein the surfactant is polysorbate 20. 
     
     
         25 . The method of  claim 18 , wherein said injection vehicle comprises a bulking agent. 
     
     
         26 . The method of  claim 25 , wherein said bulking agent comprises sorbitol. 
     
     
         27 . The method of  claim 18 , wherein said injection vehicle comprises a member selected from the group consisting of mannitol, sucrose, glucose and sorbital. 
     
     
         28 . The method of  claim 15 , wherein the composition is administered by injection. 
     
     
         29 . The method of  claim 15 , wherein the composition is administered intramuscularly or subcutaneously. 
     
     
         30 . The method of  claim 15  further comprising a second administration of the composition at least about 7 days after the first administration. 
     
     
         31 . The method of  claim 15  further comprising a second administration of the composition at least about 14 days after the first administration. 
     
     
         32 . An injectable composition for the extended release of aripiprazole consisting essentially of a suspension of at least about 10 mg/ml aripiprazole in an injection vehicle. 
     
     
         33 . The composition of  claim 32 , wherein the aripiprazole release is for at least 7 days. 
     
     
         34 . The composition of  claim 33 , wherein said injection vehicle contains carboxymethyl cellulose. 
     
     
         35 . The composition of  claim 34 , wherein said injection vehicle contains sodium carboxymethyl cellulose. 
     
     
         36 . The composition of  claim 35 , wherein said injection vehicle contains about 1% by volume sodium carboxymethyl cellulose. 
     
     
         37 . The composition of  claim 33 , wherein the injection vehicle further contains a surfactant. 
     
     
         38 . The composition of  claim 37 , wherein the surfactant is selected from the group consisting of polysorbate 20, and polysorbate 80. 
     
     
         39 . The composition of  claim 37 , wherein the surfactant is polysorbate 20. 
     
     
         40 . The composition of  claim 33 , wherein said injection vehicle contains a bulking agent. 
     
     
         41 . The composition of  claim 40 , wherein said bulking agent contains sorbitol. 
     
     
         42 . The composition of  claim 33 , wherein said injection vehicle contains a member selected from the group consisting of mannitol, sucrose, glucose and sorbital.