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 being
polyethylene glycol and carboxymethyl cellulose or a salt thereof, 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,
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 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.
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 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.
5 . 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
a suspending agent
wherein the suspending agent is polyethylene glycol and carboxymethyl cellulose or a salt thereof,
and wherein 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.
6 . (canceled)
7 . The composition according to claim 5 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.
8 . (canceled)
9 . The composition according to claim 5 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.
10 . (canceled)
11 . The composition according to claim 5 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.
12 - 25 . (canceled)
26 . 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
wherein the suspending agent is polyethylene glycol and carboxymethyl cellulose or a salt thereof,
and wherein 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,
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.
27 . The injectable preparation according to claim 28 wherein the poorly soluble drug has a mean primary particle diameter of 2 to 7 μm.
28 . 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
wherein the suspending agent is polyethylene glycol and carboxymethyl cellulose or a salt thereof,
and wherein 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,
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 of to three months.
29 . The injectable preparation according to claim 28 wherein the poorly soluble drug has a mean primary particle diameter of 5 to 20 μm.
30 . (canceled)
31 . The injectable preparation according to claim 26 wherein
the concentration of polyethylene glycol is 0.05 to 2 mg/mL, and the concentration of carboxymethyl cellulose or salt thereof being is 0.5 to 50 mg/mL.
32 - 34 . (canceled)
35 . The injectable preparation according to claim 26 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.
36 . A method for treating or preventing a recurrence of schizophrenia, bipolar disorder, or depression, the method comprising administering the injectable preparation according to claim 1 .
37 . The method according to claim 36 wherein the injectable preparation is administered intramuscularly or subcutaneously.
38 . The injectable preparation according to claim 28 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.
39 . The injectable preparation according to claim 28 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.
40 . The injectable preparation according to claim 1 wherein the suspending agent is contained at a concentration of 0.05 to 150 mg/mL.
41 . The composition according to claim 5 wherein the suspending agent is contained at a concentration of 0.05 to 150 mg/mL.
42 . The composition according to claim 26 wherein the suspending agent is contained at a concentration of 0.05 to 150 mg/mL.
43 . The composition according to claim 28 wherein the suspending agent is contained at a concentration of 0.05 to 150 mg/mL.
44 . The injectable preparation according to claim 4 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.
45 . The composition according to claim 5 wherein the 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one is the form of a dihydrate.
46 . The injectable preparation according to claim 26 wherein the 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one is the form of a dihydrate.
47 . The injectable preparation according to claim 28 wherein the 7-[4-(4-benzo[b]thiophen-4-yl-piperazin-1-yl)butoxy]-1H-quinolin-2-one is the form of a dihydrate.
48 . A method for treating or preventing a recurrence of schizophrenia, bipolar disorder, or depression, the method comprising administering the injectable preparation according to claim 26 .
49 . The method according to claim 48 wherein the injectable preparation is administered intramuscularly or subcutaneously.
50 . A method for treating or preventing a recurrence of schizophrenia, bipolar disorder, or depression, the method comprising administering the injectable preparation according to claim 28 .
51 . The method according to claim 50 wherein the injectable preparation is administered intramuscularly or subcutaneously.