Claims for Patent: 9,452,131

Summary for Patent: 9,452,131

Title:	Aripiprazole formulations having increased injection speeds
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.
Inventor(s):	Hickey; Magali B. (Westwood, MA), Vandiver; Jennifer (Arlington, MA)
Assignee:	ALKERMES PHARMA IRELAND LIMITED (Dublin, IE)
Application Number:	14/663,042
Patent Claims:	1. A method of treating schizophrenia 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): ##STR00048## wherein n is an integer between 4 and 14; (b) 0.3-0.4 weight percent sorbitan laurate; (c) 0.1-0.3 weight percent polysorbate 20; and (d) an aqueous vehicle wherein the percentages of (a), (b), and (c) are relative to the total weight of the composition; wherein the pharmaceutical composition has a total injection volume from 1.0 mL to 10 mL; and wherein the total pharmaceutical composition is continuously injected within 10 seconds at said rate. 2. The method of claim 1, wherein the said pharmaceutical composition comprises: (a) about 26.6 weight percent Compound 1: ##STR00049## (b) about 0.37 weight percent sorbitan laurate; (c) about 0.15 weight percent polysorbate 20; and (d) an aqueous vehicle wherein the percentages of (a), (b), and (c) are relative to the total weight of the composition. 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 3.4 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. 15. The method of any one of claims 1, 2, 3-9, 13, and 14, wherein the total injection volume of the pharmaceutical composition is from 1 mL to 4 mL. 16. A method of treating schizophrenia 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): ##STR00050## wherein n is an integer between 4 and 14; (b) 0.3-0.4 weight percent sorbitan laurate; (c) 0.1-0.3 weight percent polysorbate 20; and (d) an aqueous vehicle wherein the percentages of (a), (b), and (c) are relative to the total weight of the composition; and wherein the pharmaceutical composition has a total injection volume of approximately 3.4 mL, and the total pharmaceutical composition is continuously injected within 10 seconds at a rate of 0.3 mL/s to 1 mL/s. 17. The method of claim 16, wherein the said pharmaceutical composition comprises: (a) about 26.6 weight percent Compound 1: ##STR00051## (b) about 0.37 weight percent sorbitan laurate; (c) about 0.15 weight percent polysorbate 20; and (d) an aqueous vehicle wherein the percentages of (a), (b), and (c) are relative to the total weight of the composition. 18. A method of treating schizophrenia 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): ##STR00052## wherein n is an integer between 4 and 14; (b) 0.3-0.4 weight percent sorbitan laurate; (c) 0.1-0.3 weight percent polysorbate 20; and (d) an aqueous vehicle wherein the percentages of (a), (b), and (c) are relative to the total weight of the composition; and wherein the pharmaceutical composition has a total injection volume of approximately 1.6 mL, and the total pharmaceutical composition is continuously injected within 5 seconds at a rate of 0.3 mL/s to 1 mL/s. 19. The method of claim 18, wherein the said pharmaceutical composition comprises: (a) about 26.6 weight percent Compound 1: ##STR00053## (b) about 0.37 weight percent sorbitan laurate; (c) about 0.15 weight percent polysorbate 20; and (d) an aqueous vehicle wherein the percentages of (a), (b), and (c) are relative to the total weight of the composition. 20. A method of treating schizophrenia 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): ##STR00054## wherein n is an integer between 4 and 14; (b) 0.3-0.4 weight percent sorbitan laurate; (c) 0.1-0.3 weight percent polysorbate 20; and (d) an aqueous vehicle wherein the percentages of (a), (b), and (c) are relative to the total weight of the composition; and wherein the pharmaceutical composition has a total injection volume of approximately 3.2 mL, and the total pharmaceutical composition is continuously injected within 10 seconds at a rate of 0.3 mL/s to 1 mL/s. 21. The method of claim 20, wherein the said pharmaceutical composition comprises: (a) about 26.6 weight percent Compound 1: ##STR00055## (b) about 0.37 weight percent sorbitan laurate; (c) about 0.15 weight percent polysorbate 20; and (d) an aqueous vehicle wherein the percentages of (a), (b), and (c) are relative to the total weight of the composition. 22. A method of treating schizophrenia 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): ##STR00056## wherein n is an integer between 4 and 14; (b) 0.3-0.4 weight percent sorbitan laurate; (c) 0.1-0.3 weight percent polysorbate 20; and (d) an aqueous vehicle wherein the percentages of (a), (b), and (c) are relative to the total weight of the composition; and wherein the pharmaceutical composition has a total injection volume of approximately 2.4 mL, and the total pharmaceutical composition is continuously injected within 8 seconds at a rate of 0.3 mL/s to 1 mL/s. 23. The method of claim 22, wherein the said pharmaceutical composition comprises: (a) about 26.6 weight percent Compound 1: ##STR00057## (b) about 0.37 weight percent sorbitan laurate; (c) about 0.15 weight percent polysorbate 20; and (d) an aqueous vehicle wherein the percentages of (a), (b), and (c) are relative to the total weight of the composition. 24. The method of claim 1, wherein the composition has a total injection volume from 3 mL to 10 mL.