Aripiprazole formulations having increased injection speeds

• US 10,085,980 B2
• Filed: 11/11/2016
• Issued: 10/02/2018
• Est. Priority Date: 03/20/2014
• Status: Active Grant

• Current Assignee: Alkermes Pharma Ireland Limited (Alkermes plc)
• Original Assignee: Alkermes Pharma Ireland Limited (Alkermes plc)
• Inventors: Hickey, Magali B., Vandiver, Jennifer
• Primary Examiner(s): Cornet, Jean P
• Application Number:
  US15/349,243
• Publication Number:
  US 20170157117A1
• Time in Patent Office: 690 Days
• Field of Search: 514 2507
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• 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: 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 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants

Abstract

The present invention relates to pharmaceutical compositions comprising a compound of Formula (I) that are useful for the intramuscular delivery of antipsychotic drugs using rapid injection rates.

Claims

1. A method of treating depression or bipolar disorder in a subject in need thereof, comprising intramuscularly administering to said subject a therapeutically effective amount of a pharmaceutical composition at a continuous injection rate of 0.3 mL/s to 1 mL/s, wherein said pharmaceutical composition comprises:

(a) 24-30 weight percent of a compound of Formula (I);

2. The method of claim 1, wherein the said pharmaceutical composition comprises:

(a) about 26.6 weight percent Compound 1;

3. The method of claim 1, wherein the administration is instantaneous.

4. The method of claim 1, wherein the pharmaceutical composition is injected using a 20 to 23 gauge needle.

5. The method of claim 4, wherein the needle is a 20 gauge needle.

6. The method of claim 4, wherein the needle is a 21 gauge needle.

7. The method of claim 1, wherein the injection is administered to the subject in the dorsal gluteal muscle.

8. The method of claim 1, wherein the injection is administered to the subject in the deltoid muscle.

9. The method of claim 1, wherein the needle does not experience injection failure due to needle clogging.

10. The method of claim 1, wherein the method does not elicit a pain intensity above a normal threshold in the subject.

11. The method of claim 1, wherein the method does not elicit any injection site reactions in the subject above a normal threshold in the subject.

12. The method of claim 11, wherein the symptoms of the injection site reaction are selected from the group consisting of redness, tenderness, warmth, itching, pain at injection site, blistering, nodule formation, and severe skin damage.

13. The method of claim 1, wherein the total injection volume of the pharmaceutical composition is approximately 3.2 mL and the total pharmaceutical composition is injected within 10 seconds, or wherein the total injection volume of the pharmaceutical composition is approximately 1.6 mL and the total pharmaceutical composition is injected within 5 seconds.

14. The method of claim 1, wherein the intramuscular injection rate is selected from the group consisting of:

0.4 mL/s, 0.5 mL/s, 0.6 mL/s, 0.7 mL/s, 0.8 mL/s, and 0.9 mL/s.

23. The method of claim 1, wherein the composition has a total injection volume from 3 mL to 10 mL.

15. A kit for the treatment of depression or bipolar disorder, wherein the kit comprises a therapeutically effective amount of a pharmaceutical composition and further comprises instructions for intramuscular injection, wherein the instructions specify a continuous intramuscular injection within 10 seconds, wherein said pharmaceutical composition comprises:

(a) 24-30 weight percent Compound 1;

16. The kit of claim 15, wherein the said pharmaceutical composition comprises:

(a) about 26.6 weight percent Compound 1;

24. The kit of claim 15, wherein the kit further comprises a container for containing the pharmaceutical composition.

25. The kit of claim 24, wherein the container is a prefilled syringe.

17. A method of treating depression or bipolar disorder in a subject in need thereof, comprising intramuscularly injecting into said subject a therapeutically effective amount of a pharmaceutical composition, wherein said pharmaceutical composition comprises:

(a) 24-30 weight percent of a compound of Formula (I);

18. The method of claim 17, wherein the said pharmaceutical composition comprises:

(a) about 26.6 weight percent Compound 1;

19. A method of treating depression or bipolar disorder in a subject in need thereof, comprising intramuscularly injecting into said subject a therapeutically effective amount of a pharmaceutical composition, wherein said pharmaceutical composition comprises:

(a) 24-30 weight percent of a compound of Formula (I);

20. The method of claim 19, wherein the said pharmaceutical composition comprises:

(a) about 26.6 weight percent Compound 1;

21. A method of treating depression or bipolar disorder in a subject in need thereof, comprising intramuscularly injecting into said subject a therapeutically effective amount of a pharmaceutical composition, wherein said pharmaceutical composition comprises:

(a) 24-30 weight percent of a compound of Formula (I);

22. The method of claim 21, wherein the said pharmaceutical composition comprises:

(a) about 26.6 weight percent Compound 1;

26. A kit for the treatment of depression or bipolar disorder, wherein the kit comprises a therapeutically effective amount of a pharmaceutical composition and further comprises instructions for intramuscular injection, wherein the instructions specify a continuous intramuscular injection within 10 seconds, wherein said pharmaceutical composition comprises:

(a) 24-30 weight percent Compound 1;

27. The kit of claim 26, wherein the said pharmaceutical composition comprises:

(a) about 26.6 weight percent Compound 1;

28. The kit of claim 26, wherein the kit further comprises a container for containing the pharmaceutical composition.

29. The kit of claim 28, wherein the container is a prefilled syringe.