Pharmaceutical compositions having improved storage stability

• US 9,861,699 B2
• Filed: 10/13/2015
• Issued: 01/09/2018
• 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, Jr., Michael J., Pan, Zhengzheng
• Primary Examiner(s): Ward, Paul V
• Application Number:
  US14/882,069
• Publication Number:
  US 20160136279A1
• Time in Patent Office: 819 Days
• 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 method for minimizing degradation of a hydrolytically labile antipsychotic agent comprising adding to a composition comprising the antipsychotic agent and an aqueous vehicle (a) a non-ionic water insoluble or immiscible ester co-surfactant and (b) a water miscible or soluble non-ionic surfactant, wherein the antipsychotic agent is Compound 1:

2. The method of claim 1, wherein the non-ionic water insoluble or immiscible ester co-surfactant is provided in an amount sufficient to minimize degradation of the antipsychotic agent.

3. The method of claim 2, wherein the amount of the non-ionic water insoluble or immiscible ester co-surfactant sufficient to minimize degradation is 0.25-0.45 weight percent of the total composition.

4. The method of claim 2, wherein the amount of the non-ionic water insoluble or immiscible ester co-surfactant sufficient to minimize degradation is 0.3-0.4 weight percent of the total composition.

5. The method of claim 2, wherein the amount of the non-ionic water insoluble or immiscible ester co-surfactant sufficient to minimize degradation does not exceed 0.5 weight percent of the total composition.

6. The method of claim 2, wherein the non-ionic water insoluble or immiscible ester co-surfactant is provided in an amount providing less than 50 parts per million of the hydrolyzed antipsychotic agent degradation product after the total composition stands for at least 24 months.

7. The method of claim 2, wherein the degradation of the hydrolytically labile antipsychotic agent is minimized at temperatures selected from any of 25°

C. -40°

C., over a time period selected from any of 1 month -24 months.

8. The method 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.

9. The method of claim 8, 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.

10. The method of claim 8, wherein the sorbitan ester is sorbitan laurate.

11. The method of claim 9, wherein the polyoxyethylene derivative of a sorbitan ester is polysorbate 20.

12. The method of claim 1, wherein the hydrolysis product is one of the following compounds: