Aripiprazole complex formulation and method

• US 7,550,445 B2
• Filed: 06/14/2006
• Issued: 06/23/2009
• Est. Priority Date: 08/20/2002
• Status: Expired due to Fees

• Current Assignee: Otsuka Pharmaceutical Company Limited (Otsuka Holdings Company Limited)
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Nerurkar, Manoj, Naringrekar, Vijay
• Primary Examiner(s): Maier; Leigh C
• Application Number:
  US11/452,782
• Publication Number:
  US 20060234979A1
• Time in Patent Office: 1,105 Days
• Field of Search: None
• US Class Current: 514/58
• 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 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/6951 using cyclodextrin cyclodextrins used as simple excipients A61K47/40
• 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: 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
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

An aripiprazole formulation is provided which includes the antipsychotic agent aripiprazole in the form of an inclusion complex in a β-cyclodextrin, preferably, sulfobutyl ether β-cyclodextrin (SBECD), which in the form of an injectable produces reversible generally minimal to mild irritation at the intramuscular injection site. A method for minimizing or reducing irritation caused by aripiprazole at an intramuscular injection site and a method for treating schizophrenia employing the above formulation are also provided.

Claims

1. An aqueous injectable formulation comprising

a) a complex comprising aripiprazole and sulfobutyl ether-β

-cyclodextrin;

b) tartaric acid;

c) sodium hydroxide; and

d) water for injection.

2. The formulation as defined in claim 1 which contains 2 mg aripiprazole/ml, 5 mg aripiprazole/ml or 7.5 mg aripiprazole/ml.

3. The formulation as defined in claim 1 having a pH of about 4.3.

4. The formulation as defined in claim 1 comprising from about 0.1 to about 2.5% by weight aripiprazole.

5. The formulation as defined in claim 1 comprising from about 0.2 to about 1.5% by weight aripiprazole.

6. The formulation as defined in claim 1 wherein the sulfobutyl ether-β

-cyclodextrin is present in an amount from about 100 to about 700 mg/ml of solution.

7. The formulation as defined in claim 1 wherein the tartaric acid is present in an amount from about 7 to about 9 mg/ml.

8. The formulation as defined in claim 1 wherein the tartaric acid and the sodium hydroxide are present in amounts to impart a pH of about 4.3 to the formulation.