Methods for administering aripiprazole

• US 8,338,428 B2
• Filed: 03/15/2012
• Issued: 12/25/2012
• Est. Priority Date: 08/06/2003
• Status: Expired due to Term

• 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:
  US13/420,822
• Publication Number:
  US 20120289516A1
• Time in Patent Office: 285 Days
• Field of Search: 514/253.07, 514/327, 514/253.01, 514/252.13, 424/400
• 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 matrices for the extended release of aripiprazole comprising a suspension of about 50 mg or more aripiprazole in an injection vehicle optionally comprising a viscosity enhancing agent, wherein the concentration of aripiprazole in the injectable composition is about 30 mg/ml or more wherein upon injection of the composition into an individual, the aripiprazole is present in the plasma of the individual for about 7 days or more.

2. The composition of claim 1, wherein aripiprazole is present in the plasma of the individual for about 21 days or more.

3. The composition of claim 1, comprising a viscosity enhancing agent wherein the viscosity enhancing agent comprises carboxymethyl cellulose.

4. The composition of claim 3, wherein said injection vehicle comprises about 1% or more 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 1, wherein the injection vehicle further comprises a wetting agent.

7. The composition of claim 6, wherein the wetting agent 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 1, 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 1, 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.

17. A method of administering aripiprazole to an individual in an extended release formulation comprising injecting the composition of claim 1 into the individual.

18. The method of claim 17, wherein aripiprazole is present in the plasma of the individual for about 21 days or more.

19. The method of claim 17, wherein the composition is administered by intramuscular injection or subcutaneous injection.

20. The method of claim 17, wherein the composition is administered every 7 days.

21. The method of claim 17, wherein the composition is administered every 14 days.

22. The composition of claim 1, wherein aripiprazole is present in the suspension as a drug particle and wherein the drug particle has a mass mean diameter of about 100 microns or less.

15. A composition comprising a suspension of about 50 mg or more of aripiprazole and an aqueous injection vehicle comprising water, a viscosity enhancing agent, a wetting agent, and a tonicity agent wherein the composition is free of sustained release materials and wherein the concentration of aripiprazole in the composition is about 30 mg/ml or more wherein upon injection of the composition into an individual, the aripiprazole is present in the plasma of the individual for about 7 days or more.

16. The composition of claim 15 wherein the injection vehicle comprises about 3% by volume carboxymethylcellulose, about 0.1% polysorbate 20 and about 1% by weight sodium chloride.