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.

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.