Claims for Patent: 10,517,951

Summary for Patent: 10,517,951

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:	US16/156,958
Patent Claims:	1. An injectable preparation suitable for the treatment of a human patient comprising a composition comprising a poorly soluble drug, a dispersion medium, and a suspending agent, the poorly soluble drug being aripiprazole or a salt thereof, or 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one or a salt thereof, the suspending agent containing polyvinylpyrrolidone, polyethylene glycol, and carboxymethyl cellulose or a salt thereof, K value of polyvinylpyrrolidone being 17, and the concentration of polyvinylpyrrolidone being 4 mg/mL, the polyethylene glycol being polyethylene glycol 400, and the concentration of polyethylene glycol being 1 mg/mL, the concentration of carboxymethyl cellulose or a salt thereof being 5 mg/mL, the poorly soluble drug being contained in a concentration of 300 mg/mL, and the composition having 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 having 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., wherein the injectable preparation is 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. The injectable preparation according to claim 1 wherein the 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one is in the form of a dihydrate. 4. The injectable preparation according to claim 1 wherein the poorly soluble drug has a mean primary particle diameter of 1 to 10 μm. 5. The injectable preparation according to claim 1 wherein the injectable preparation is disposed within a container. 6. The injectable preparation according to claim 5 wherein the container is syringe or vial. 7. A gel composition suitable for the treatment of a human patient comprising a poorly soluble drug which is aripiprazole or a salt thereof, or 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one or a salt thereof, water, and a suspending agent wherein the suspending agent contains polyvinylpyrrolidone, polyethylene glycol, and carboxymethyl cellulose or a salt thereof, the poorly soluble drug has a mean primary particle diameter of 0.5 to 30 μm and is contained in a concentration of 300 mg/mL, K value of polyvinylpyrrolidone is 17, and the concentration of polyvinylpyrrolidone is 4 mg/mL, the polyethylene glycol is polyethylene glycol 400, and the concentration of polyethylene glycol is 1 mg/mL, the concentration of carboxymethyl cellulose or a salt thereof is 5 mg/mL, and the composition is in gel form for storage and forms a sol when subjected to an impact. 8. The composition according to claim 7 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. 9. The composition according to claim 7 which 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 which 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. 10. The composition according to claim 7 wherein the 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one is in the form of a dihydrate. 11. The composition according to claim 7 wherein the poorly soluble drug has a mean primary particle diameter of 1 to 10 μm. 12. The composition according to claim 7 wherein the composition is disposed within a container. 13. The composition according to claim 12 wherein the container is syringe or vial. 14. A sustained release injectable preparation suitable for the treatment of a human patient comprising a composition comprising a poorly soluble drug which is aripiprazole or a salt thereof, or 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one or a salt thereof, water, and a suspending agent comprising polyvinylpyrrolidone, polyethylene glycol, and carboxymethyl cellulose or a salt thereof, wherein the poorly soluble drug has a mean primary particle diameter of 1 to 10 μm and is contained in a concentration of 300 mg/mL, K value of polyvinylpyrrolidone is 17, and the concentration of polyvinylpyrrolidone is 4 mg/mL, the polyethylene glycol is polyethylene glycol 400, and the concentration of polyethylene glycol is 1 mg/mL, and the concentration of carboxymethyl cellulose or a salt thereof is 5 mg/mL, the preparation being in the form of a gel when allowed to stand, and changing to a sol when subjected to an impact, and the preparation being administered once per month. 15. The injectable preparation according to claim 14 wherein the poorly soluble drug has a mean primary particle diameter of 2 to 7 μm. 16. A sustained release injectable preparation comprising a composition comprising a poorly soluble drug which is aripiprazole or a salt thereof, or 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one or a salt thereof, water, and a suspending agent comprising polyvinylpyrrolidone, polyethylene glycol, and carboxymethyl cellulose or a salt thereof, wherein the poorly soluble drug has a mean primary particle diameter of 4 to 30 μm and is contained in a concentration of 300 mg/mL, K value of polyvinylpyrrolidone is 17, and the concentration of polyvinylpyrrolidone is 4 mg/mL, the polyethylene glycol is polyethylene glycol 400, and the concentration of polyethylene glycol is 1 mg/mL, and the concentration of carboxymethyl cellulose or a salt thereof is 5 mg/mL, the preparation being in the form of a gel when allowed to stand, and changing to a sol when subjected to an impact, and the preparation being administered once every two to three months. 17. The injectable preparation according to claim 16 wherein the poorly soluble drug has a mean primary particle diameter of 5 to 20 μm. 18. The injectable preparation according to claim 14 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. 19. The injectable preparation according to claim 14 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. 20. The injectable preparation according to claim 14 wherein the 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one is in the form of a dihydrate. 21. The injectable preparation according to claim 14 wherein the preparation being disposed within a container. 22. The injectable preparation according to claim 21 wherein the container is syringe or vial. 23. The injectable preparation according to claim 16 wherein the preparation being disposed within a container. 24. The injectable preparation according to claim 23 wherein the container is syringe or vial. 25. A method for treating schizophrenia, bipolar disorder, or depression, the method comprising administering the injectable preparation according to claim 1. 26. The method according to claim 25 wherein the injectable preparation is administered intramuscularly or subcutaneously.