Aripiprazole formulations having increased injection speeds

• US 10,238,651 B2
• Filed: 08/29/2018
• Issued: 03/26/2019
• 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:
  US16/116,652
• Publication Number:
  US 20180369239A1
• Time in Patent Office: 209 Days
• 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 bipolar disorder, depression, or schizophrenia in a subject in need thereof, comprising intramuscularly administering to said subject a therapeutically effective amount of a pharmaceutical composition at a rapid and continuous injection rate, 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 total volume of the pharmaceutical composition is approximately 3.2 mL, 2.4 mL, or 1.6 mL.

12. The method of claim 1, wherein approximately 3.2 mL of the pharmaceutical composition is injected within 10 seconds, or wherein approximately 2.4 mL of the pharmaceutical composition is injected within 8 seconds, or wherein approximately 1.6 mL of the pharmaceutical composition is injected within 5 seconds.

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

0.3 mL/s, 0.35 mL/s, 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.

24. The method of claim 1, wherein the method comprises treating depression.

14. A method of treating schizophrenia in a subject in need thereof, comprising intramuscularly administering to said subject a therapeutically amount of a pharmaceutical composition at a rapid and continuous intramuscular injection rate, wherein said pharmaceutical composition comprises:

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

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

0.3 mL/s, 0.35 mL/s, 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.

16. The method of claim 14, wherein the total volume of the pharmaceutical composition is approximately 3.2 mL, 2.4 mL, or 1.6 mL.

17. The method of claim 14, wherein approximately 3.2 mL of the pharmaceutical composition is injected within 10 seconds, or wherein approximately 2.4 mL of the pharmaceutical composition is injected within 8 seconds, or wherein approximately 1.6 mL of the pharmaceutical composition is injected within 5 seconds.

25. The method of claim 14, wherein the said pharmaceutical composition comprises:

(a) about 26.6 weight percent Compound 1;

26. The method of claim 25, wherein the total volume of the pharmaceutical composition is approximately 3.2 mL, 2.4 mL, or 1.6 mL.

27. The method of claim 25, wherein approximately 3.2 mL of the pharmaceutical composition is injected within 10 seconds, or wherein approximately 2.4 mL of the pharmaceutical composition is injected within 8 seconds, or wherein approximately 1.6 mL of the pharmaceutical composition is injected within 5 seconds.

28. The method of claim 25, wherein the intramuscular injection rate is selected from the group consisting of:

0.3 mL/s, 0.35 mL/s, 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.

18. A kit useful for the treatment of bipolar disorder, depression, or schizophrenia, wherein the kit comprises a therapeutically effective amount of a pharmaceutical composition and further comprises instructions for intramuscular injection, wherein the instructions specify a rapid and continuous intramuscular injection rate, wherein said pharmaceutical composition comprises:

(a) 24-30 weight percent Compound 1;

19. The kit according to claim 18, wherein the kit is adapted to be associated with a treatment regimen.

20. The kit of claim 18, wherein the said pharmaceutical composition comprises:

(a) about 26.6 weight percent Compound 1;

21. The kit of claim 18, wherein the intramuscular injection rate is selected from the group consisting of:

0.3 mL/s, 0.35 mL/s, 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.

22. The kit of claim 18, wherein the total volume of the pharmaceutical composition is approximately 3.2 mL, 2.4 mL, or 1.6 mL.

23. The kit of claim 18, wherein approximately 3.2 mL of the pharmaceutical composition is injected within 10 seconds, or wherein approximately 2.4 mL of the pharmaceutical composition is injected within 8 seconds, or wherein approximately 1.6 mL of the pharmaceutical composition is injected within 5 seconds.

29. The kit of claim 18, wherein the kit is useful for the treatment of bipolar disorder.

30. The kit of claim 18, wherein the kit is useful for the treatment of depression.

31. The kit of claim 18, wherein the kit is useful for the treatment of schizophrenia.

32. A method of treating bipolar disorder in a subject in need thereof, comprising intramuscularly administering to said subject a therapeutically amount of a pharmaceutical composition at a rapid and continuous intramuscular injection rate, wherein said pharmaceutical composition comprises:

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

33. The method of claim 32, wherein the total volume of the pharmaceutical composition is approximately 3.2 mL, 2.4 mL, or 1.6 mL.

34. The method of claim 32, wherein approximately 3.2 mL of the pharmaceutical composition is injected within 10 seconds, or wherein approximately 2.4 mL of the pharmaceutical composition is injected within 8 seconds, or wherein approximately 1.6 mL of the pharmaceutical composition is injected within 5 seconds.

35. The method of claim 32, wherein the intramuscular injection rate is selected from the group consisting of:

0.3 mL/s, 0.35 mL/s, 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.

36. The method of claim 32, wherein the said pharmaceutical composition comprises:

(a) about 26.6 weight percent Compound 1;