Methods for administering aripiprazole

• US 8,338,427 B2
• Filed: 10/15/2008
• Issued: 12/25/2012
• Est. Priority Date: 08/06/2003
• Status: Active Grant

• Current Assignee: Otsuka Pharmaceutical Company Limited (Otsuka Holdings Company Limited)
• Original Assignee: Alkermes Pharma Ireland Limited (Alkermes plc)
• Inventors: Brown, Josiah
• Primary Examiner(s): FISHER, ABIGAIL L
• Application Number:
  US12/251,656
• Publication Number:
  US 20090143403A1
• Time in Patent Office: 1,532 Days
• Field of Search: 424/400, 514/253.07, 514/327, 514/252.13, 514/253.01
• US Class Current: 514/253.07
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/10 Dispersions; Emulsions A61K9/06 takes precedence; composition of dispersions, emulsions A61K47/00
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

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.

Claims

1. An injectable composition that is free of sustained release materials for the extended release of aripiprazole comprising a suspension of at least about 10 mg/ml of aripiprazole in an injection vehicle optionally comprising a viscosity enhancing agent and wherein the aripiprazole release is for at least 7 days.

2. The composition of claim 1, wherein the viscosity enhancing agent comprises carboxymethyl cellulose.

3. The composition of claim 1, wherein said injection vehicle further comprises a wetting agent.

4. The composition of claim 3, wherein the wetting agent is selected from the group consisting of polysorbate 20, polysorbate 40, and polysorbate 80.

5. The composition of claim 1, wherein said injection vehicle comprises a density enhancing agent.

6. The composition of claim 5, wherein said density enhancing agent comprises sorbitol.

7. The composition of claim 1, wherein said injection vehicle comprises a tonicity adjusting agent.

8. The composition of claim 7, wherein said tonicity adjusting agent comprises sodium chloride.

9. A composition comprising a suspension of 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 wherein upon administration of the composition the aripiprazole release is for at least 7 days.

10. A composition comprising a suspension of 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 0.9% by weight to about 1% by weight sodium chloride wherein upon administration of the composition the aripiprazole release is for at least 7 days.

21. A method for providing aripiprazole to an individual in an extended release injectable composition comprising administering a composition of claim 10.

11. A method for providing aripiprazole to an individual in an extended release injectable composition that is free of sustained release materials comprising administering a mixture of at least about 10 mg/ml of aripiprazole in an injection vehicle optionally comprising a viscosity enhancing agent and wherein a therapeutically effective amount of the aripiprazole is present in the plasma of the individual for at least about 7 days.

12. The method of claim 11, wherein the viscosity enhancing agent comprises carboxymethyl cellulose.

13. The method of claim 11, wherein the injection vehicle further comprises a wetting agent.

14. The method of claim 13, wherein the wetting agent is selected from the group consisting of polysorbate 20, polysorbate 40, and polysorbate 80.

15. The method of claim 11, wherein said injection vehicle comprises a density enhancing agent.

16. The method of claim 15, wherein said density enhancing agent comprises sorbitol.

17. The method of claim 11, wherein said injection vehicle comprises a tonicity adjusting agent.

18. The method of claim 17, wherein said tonicity adjusting agent comprises sodium chloride.

19. The method of claim 11, wherein the composition is administered by injection selected from the group consisting of:

intramuscular injection or subcutaneous injection.

20. The method of claim 11 further comprising a second administration of the composition selected from the group consisting of:

at least about 7 days after first administration and at least about 14 days after the first administration.