Pharmaceutical compositions having improved storage stability

• US 10,639,376 B2
• Filed: 05/29/2019
• Issued: 05/05/2020
• 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:
  US16/425,150
• Publication Number:
  US 20190275155A1
• Time in Patent Office: 342 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 and/or immiscible ester co-surfactant and (b) a water miscible and/or soluble non-ionic surfactant, wherein the antipsychotic agent is Compound 1:

2. The method of claim 1, wherein the amount of sorbitan laurate sufficient to minimize degradation is 0.25-0.45 weight percent of the total composition.

3. The method of claim 1, wherein the amount of sorbitan laurate sufficient to minimize degradation is 0.3-0.4 weight percent of the total composition.

9. The method of claim 1, wherein 0.3-0.4 weight percent sorbitan laurate and 0.1-0.3 weight percent polysorbate 20 are added to the composition, and wherein the composition comprises 24-30 weight percent Compound 1:

10. The method of claim 1, wherein about 0.37 weight percent sorbitan laurate and about 0.15 weight percent polysorbate 20 are added to the composition, and wherein the composition comprises about 26.6 weight percent Compound 1:

4. A method for the preparation of an aqueous pharmaceutical composition comprising:

(a) 24-30 weight percent Compound 1;

5. The method of claim 4, wherein the composition is in a ready to use form.

6. The method of claim 4, wherein hydrolysis product is one of the following compounds:

7. A method for treating disorders of the central nervous system, comprising administering an effective amount of a composition formed by the method of claim 4 to an individual in need of such treatment.

8. The method of claim 7, wherein the pharmaceutical composition comprises:

(a) about 26.6 weight percent Compound 1;

11. The method of claim 6, wherein the pharmaceutical composition comprises less than 50 parts per million of the hydrolysis product after standing for at least 12 months.

12. The method of claim 6, wherein the pharmaceutical composition comprises less than 50 parts per million of the hydrolysis product after standing for at least 24 months.

13. The method of claim 6, wherein the pharmaceutical composition comprises less than 30 parts per million of the hydrolysis product.

14. The method of claim 11, wherein the pharmaceutical composition comprises less than 30 parts per million of the hydrolysis product after standing for at least 24 months.

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

16. The method of claim 8, wherein the pharmaceutical composition is administered as a single, undivided dose.

17. The method of claim 8, wherein the disorder of the central nervous system is schizophrenia.

18. The method of claim 8, wherein the disorder of the central nervous system is bipolar disorder.

19. The method of claim 8, wherein the disorder of the central nervous system is depression.