Pharmaceutical compositions having improved storage stability

• US 9,193,685 B2
• Filed: 09/19/2013
• Issued: 11/24/2015
• Est. Priority Date: 09/19/2012
• Status: Active Grant

• Current Assignee: Alkermes Pharma Ireland Limited (Alkermes plc)
• Original Assignee: Alkermes Pharma Ireland Limited (Alkermes plc)
• Inventors: Perry, Jason M., Deaver, Daniel R., Hickey, Magali B., Remenar, Julius F., Vandiver, Jennifer, Palmieri, Michael J. Jr., Pan, Zhengzheng
• Primary Examiner(s): Ward, Paul V
• Application Number:
  US14/031,842
• Publication Number:
  US 20140088115A1
• Time in Patent Office: 796 Days
• Field of Search: 514/253.07
• US Class Current: 1/1
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• 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 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 25/24 Antidepressants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 215/227 only one oxygen atom which is attached in position 2

Abstract

The present invention relates to a pharmaceutical composition that provides long-term stability of a hydrolytically labile antipsychotic agent

Claims

1. A pharmaceutical composition comprising:

(a) a hydrolytically labile antipsychotic agent;

(b) a non-ionic water insoluble or immiscible ester co-surfactant;

(c) a water miscible or soluble non-ionic surfactant; and

(d) an aqueous vehicle;

wherein the pharmaceutical composition comprises less than 50 parts per million of the hydrolysis product of the antipsychotic agent.

2. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises less than 30 parts per million of the hydrolyzed antipsychotic agent.

3. The pharmaceutical composition of claim 1, wherein the non-ionic water insoluble or immiscible ester co-surfactant is a sorbitan ester of a carboxylic acid, wherein the carboxylic acid comprises 4-20 carbon atoms.

4. The pharmaceutical composition of claim 1, wherein the water miscible or soluble non-ionic surfactant is a polyoxyethylene derivative of a sorbitan ester of a carboxylic acid, wherein the carboxylic acid comprises 8-14 carbon atoms.

5. The pharmaceutical composition of claim 1, wherein the antipsychotic agent is Compound 1

6. The pharmaceutical composition of claim 5, wherein the hydrolysis product is of one or more of the following formulas:

7. The pharmaceutical composition of claim 1, wherein the water miscible or soluble non-ionic surfactant is a polyoxyethylene derivative of a sorbitan ester of a carboxylic acid, wherein the carboxylic acid comprises 8-14 carbon atoms.

8. The pharmaceutical composition of claim 7, wherein the sorbitan ester is sorbitan laurate.

11. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises less than 50 parts per million of the hydrolysis product of the antipsychotic agent after standing for at least 12 months.

12. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises less than 50 parts per million of the hydrolysis product of the antipsychotic agent after standing for at least 24 months.

13. The pharmaceutical composition of claim 1, wherein the non-ionic water insoluble or immiscible ester co-surfactant is sorbitan laurate, and wherein the water miscible or soluble non-ionic surfactant is polysorbate 20.

14. A method for treating a disorder of the central nervous system, comprising administering an effective amount of the composition of claim 1 to an individual in need of such treatment, wherein the disorder of the central nervous system is schizophrenia or bipolar disorder.

9. A pharmaceutical composition comprising:

(a) 24-30 weight percent Compound 1;

10. A pharmaceutical composition comprising:

(a) about 26.6 weight percent Compound 1;