Injectable preparation
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.
1. An injectable preparation comprising a composition comprising a poorly soluble drug, a dispersion medium, and a suspending agent, the suspending agent containing polyvinylpyrrolidone, 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 5° C., 25° C. or 40° C.,
wherein the poorly soluble drug 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,
the poorly soluble drug has a mean primary particle diameter of 30 μm or less and is contained in a concentration of 200 to 600 mg/mL, and
K value of polyvinylpyrrolidone is 12 to 30, and the concentration of polyvinylpyrrolidone is 0.1 to 100 mg/mL.
2. The injectable preparation according to claim 1 , 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 to0.02 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.
3. The injectable preparation according to claim 1 comprising a composition comprising at least water as a dispersion medium.
4. The injectable preparation according to claim 1 , wherein the suspending agent further contains polyethylene glycol.
5. The injectable preparation according to claim 1 , wherein the suspending agent further contains polyethylene glycol and carboxymethyl cellulose or a salt thereof.
6. A gel 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
suspending agent,
wherein the suspending agent contains 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, and
K value of polyvinylpyrrolidone is 12 to 30, and the concentration of polyvinylpyrrolidone is 0.1 to 100 mg/mL.
7. The composition according to claim 6 , wherein the suspending agent further contains polyethylene glycol.
8. The composition according to claim 6 , wherein the suspending agent further contains polyethylene glycol and carboxymethyl cellulose or a salt thereof.
9. The composition according to claim 8 , wherein the concentration of polyethylene glycol is 0.05 to 2 mg/mL, and the concentration of carboxymethyl cellulose or a salt thereof is 0.5 to 50 mg/m L.
10. The composition according to claim 6 , 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.
11. The composition according to claim 6 , 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 5° C., 25° C. or 40° C.
12. The composition according to claim 6 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.
13. 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
suspending agent,
wherein the suspending agent contains polyvinylpyrrolidone,
the poorly soluble drug has a mean primary particle diameter of 1 to 10 μm and is contained in a concentration of 200 to 400 mg/mL, and
K value of polyvinylpyrrolidone is 12 to 30, and the concentration of polyvinylpyrrolidone is 0.1 to 100 mg/mL,
the composition 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.
14. The injectable preparation according to claim 13 , wherein the poorly soluble drug has a mean primary particle diameter of 2 to 7 μm.
15. 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
suspending agent,
wherein the suspending agent contains polyvinylpyrrolidone,
the poorly soluble drug has a mean primary particle diameter of 4 to 30 μm and is contained in a concentration of 300 to 600 mg/mL, and
K value of polyvinylpyrrolidone is 12 to 30, and the concentration of polyvinylpyrrolidone is 0.1 to 100 mg/mL,
the composition 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.
16. The injectable preparation according to claim 15 , wherein the poorly soluble drug has a mean primary particle diameter of 5 to 20 μm.
17. The injectable preparation according to claim 13 , wherein the suspending agent further contains polyethylene glycol.
18. The injectable preparation according to claim 13 , wherein the suspending agent further contains polyethylene glycol and carboxymethyl cellulose or a salt thereof.
19. The injectable preparation according to claim 18 , wherein the concentration of polyethylene glycol is 0.05 to 2 mg/mL, and the concentration of carboxymethyl cellulose or a salt thereof is 0.5 to 50 mg/mL.
20. The injectable preparation according to claim 13 , 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.
21. The injectable preparation according to claim 13 , 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 5° C., 25° C. or 40° C.
22. The injectable preparation according to claim 13 , 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.
23. A method for treating a recurrence of schizophrenia, bipolar disorder, or depression, the method comprising administering the injectable preparation according to claim 1 .
24. The method according to claim 23 , wherein the injectable preparation is administered intramuscularly or subcutaneously.