Claims for Patent: 11,638,757

Summary for Patent: 11,638,757

Title:	Injectable preparation
Abstract:	An object of the present invention is to provide a storage-stable injectable preparation comprising a composition comprising a poorly soluble drug as an active ingredient and a dispersion medium. Another object of the present invention is to provide a compact, lightweight prefilled syringe by filling a syringe with the injectable preparation. The present invention provides an injectable preparation comprising a composition comprising a poorly soluble drug, a dispersion medium, and a specific suspending agent, the composition having a viscosity of 40 pascal-seconds or more in at least one point in the shear rate range of 0.01 to 0.02 s−1 and having a viscosity of 0.2 pascal-seconds or less in at least one point in the shear rate range of 900 to 1,000 s−1, as measured.
Inventor(s):	Daiki Kaneko, Takakuni Matsuda, Yusuke Hoshika
Assignee:	Otsuka Pharmaceutical Co Ltd
Application Number:	US17/444,469
Patent Claims:	1. An injectable preparation comprising a composition comprising aripiprazole or a salt thereof, a dispersion medium, and a suspending agent, the suspending agent comprises polyvinylpyrrolidone, wherein the aripiprazole or a salt thereof has a mean primary particle diameter of 30 μm or less and is contained in a concentration of 200 to 600 mg/mL, which is calculated as an anhydrate, the K value of polyvinylpyrrolidone is 12 to 30, and the concentration of polyvinylpyrrolidone is 0.1 to 100 mg/mL, wherein the composition has a viscosity of 40 Pa·s or more in at least one point in the shear rate range of 0.01 to 0.02 s−1 and has a viscosity of 0.2 Pa·s or less in at least one point in the shear rate range of 900 to 1,000 s−1, as measured by a rheometer at 25° C., and the injectable preparation is disposed within a prefilled syringe in gel form for storage and forms a sol when subjected to an impact. 2. The injectable preparation according to claim 1, comprising a composition comprising at least water as a dispersion medium. 3. A sustained release injectable preparation comprising a composition comprising a poorly soluble drug which is aripiprazole or a salt thereof, water, and suspending agent, wherein the suspending agent comprises polyvinylpyrrolidone, the poorly soluble drug has a mean primary particle diameter of 0.5 to 30 μm and is contained in a concentration of 200 to 600 mg/mL, which is calculated as an anhydrate, and K value of polyvinylpyrrolidone is 12 to 30, and the concentration of polyvinylpyrrolidone is 0.1 to 100 mg/mL, wherein the composition has a viscosity of 40 Pa·s or more in at least one point in the shear rate range of 0.01 to 0.02 s−1 and has a viscosity of 0.2 Pa·s or less in at least one point in the shear rate range of 900 to 1,000 s−1, as measured by a rheometer at 25° C., and the composition being in the form of a gel when allowed to stand, and changing to a sol when subjected to an impact. 4. The injectable preparation according to claim 3, wherein the poorly soluble drug has a mean primary particle diameter of 1 to 10 μm. 5. The injectable preparation according to claim 3, wherein the poorly soluble drug has a mean secondary particle diameter that is up to but not exceeding three times the mean primary particle diameter thereof. 6. A method for treating a recurrence of schizophrenia, bipolar disorder, or depression, the method comprising administering the injectable preparation according to claim 1. 7. The method according to claim 6 wherein the injectable preparation is administered intramuscularly or subcutaneously. 8. The injectable preparation according to claim 1, wherein the aripiprazole or a salt thereof has a mean primary particle diameter of 1 to 10 μm. 9. The injectable preparation according to claim 1, wherein the aripiprazole or a salt thereof has a mean secondary particle diameter that is up to but not exceeding three times the mean primary particle diameter thereof. 10. The injectable preparation according to claim 1, wherein the polyvinylpyrrolidone has a K value of 12 to 20. 11. The injectable preparation according to claim 1, wherein the concentration of polyvinylpyrrolidone is 0.5 to 20 mg/mL. 12. The injectable preparation according to claim 1, wherein the suspending agent further contains polyethylene glycol. 13. The injectable preparation according to claim 1, wherein the suspending agent further contains polyethylene glycol and carboxymethyl cellulose or a salt thereof. 14. The injectable preparation according to claim 1, wherein the aripiprazole or salt thereof is present at a concentration of 250 to 450 mg/mL. 15. The injectable preparation according to claim 13, wherein the concentration of polyethylene glycol is 0.1 to 100 mg/mL, and the concentration of carboxymethyl cellulose or a salt thereof is 0.5 to 50 mg/mL. 16. The injectable preparation according to claim 13, wherein the injectable preparation comprises: 2 to 20 mg/mL polyvinylpyrrolidone; 0.1 to 50 mg/mL polyethylene glycol; and 2 to 20 mg/mL carboxymethyl cellulose or a salt thereof. 17. The method according to claim 6, wherein the injectable preparation is administered once every two to three months. 18. The injectable preparation according to claim 12, wherein the polyethylene glycol is polyethylene glycol 400, and the polyethylene glycol 400 is present at a concentration of 0.5 to 5 mg/mL. 19. The injectable preparation according to claim 12, wherein the polyethylene glycol is polyethylene glycol 4000, and the polyethylene glycol 4000 is present at a concentration of 0.1 to 40 mg/mL. 20. The injectable preparation according to claim 1, wherein the aripiprazole or a salt thereof is stable with respect to precipitation for the indicated shelf life of the preparation. 21. The injectable preparation according to claim 3, wherein the polyvinylpyrrolidone has a K value of 12 to 20. 22. The injectable preparation according to claim 3, wherein the concentration of polyvinylpyrrolidone is 0.5 to 20 mg/mL. 23. The injectable preparation according to claim 3, wherein the suspending agent further contains polyethylene glycol. 24. The injectable preparation according to claim 3, wherein the suspending agent further contains polyethylene glycol and carboxymethyl cellulose or a salt thereof. 25. The injectable preparation according to claim 3, wherein the poorly soluble drug is present at a concentration of 250 to 450 mg/mL. 26. The injectable preparation according to claim 24, wherein the concentration of polyethylene glycol is 0.1 to 100 mg/mL, and the concentration of carboxymethyl cellulose or a salt thereof is 0.5 to 50 mg/mL. 27. The injectable preparation according to claim 24, wherein the injectable preparation comprises: 2 to 20 mg/mL polyvinylpyrrolidone; 0.1 to 50 mg/mL polyethylene glycol; and 2 to 20 mg/mL carboxymethyl cellulose or a salt thereof. 28. A method for treating a recurrence of schizophrenia, bipolar disorder, or depression, the method comprising administering the injectable preparation according to claim 3. 29. The method according to claim 28, wherein the injectable preparation is administered intramuscularly or subcutaneously. 30. The method according to claim 28, wherein the injectable preparation is administered once every two to three months. 31. The injectable preparation according to claim 23, wherein the polyethylene glycol is polyethylene glycol 400, and the polyethylene glycol 400 is present at a concentration of 0.5 to 5 mg/mL. 32. The injectable preparation according to claim 23, wherein the polyethylene glycol is polyethylene glycol 4000, and the polyethylene glycol 400 is present at a concentration of 0.1 to 40 mg/mL. 33. The injectable preparation according to claim 3, wherein the aripiprazole or a salt thereof is stable with respect to precipitation for the indicated shelf life of the preparation. 34. The injectable preparation according to claim 1 wherein the aripiprazole or a salt thereof is a monohydrate of aripiprazole or a salt thereof. 35. The injectable preparation according to claim 3 wherein the aripiprazole or a salt thereof is a monohydrate of aripiprazole or a salt thereof.