Depot formulations

Abstract

Pharmaceutical compositions comprising an active pharmaceutical ingredient, a high viscosity liquid carrier material, a hydrophobic solvent, and a hydrophilic solvent are disclosed. Also disclosed are methods of manufacturing and using the compositions. The compositions are suitable for use, e.g., as depot formulations.

1 . A composition comprising:
 sirolimus present in an amount ranging from about 1 wt % to about 5 wt %, based on weight of the composition;   sucrose acetate isobutyrate (SAIB) present in an amount ranging from about 0.5 wt % to about 5 wt %, based on weight of the composition;   benzyl benzoate present in an amount ranging from about 35 wt % to about 50 wt %, based on weight of the composition;   ethanol present in an amount ranging from about 1 wt % to about 10 wt %, based on weight of the composition;   polyethylene glycol (PEG) present in an amount ranging from about 40 wt % to about 50 wt %, based on weight of the composition; and   vitamin E in an amount ranging from about 0.01 wt % to about 5 wt %.   
     
     
         2 .- 9 . (canceled) 
     
     
         10 . The composition of  claim 1 , wherein the benzyl benzoate is present in an amount ranging from about 35 wt % to about 45 wt %, based on weight of the composition. 
     
     
         11 .- 15 . (canceled) 
     
     
         16 . The composition of  claim 1 , wherein the ethanol is present in an amount ranging from about 1 wt % to about 7 wt %, based on weight of the composition. 
     
     
         17 .- 24 . (canceled) 
     
     
         25 . The composition of  claim 1 , wherein the vitamin E is present in an amount ranging from about 0.1 wt % to about 5 wt %, based on weight of the composition. 
     
     
         26 . The composition of  claim 1 , wherein the vitamin E is present in an amount ranging from about 0.5 wt % to about 2 wt %, based on weight of the composition. 
     
     
         27 . The composition of  claim 1 , wherein the composition has a weight ratio of SAIB:vitamin E ranging from about 0.5 to about 10. 
     
     
         28 .- 29 . (canceled) 
     
     
         30 . The composition of  claim 1 , the composition consisting essentially of:
 sirolimus in an amount ranging from about 1 wt % to about 5 wt %, based on weight of the composition;   SAIB in an amount ranging from about 0.1 wt % to about 10 wt %, based on weight of the composition;   benzyl benzoate in an amount ranging from about 30 wt % to about 45 wt %, based on weight of the composition;   ethanol in an amount ranging from about 1 wt % to about 10 wt %, based on weight of the composition;   PEG400 in an amount ranging from about 40 wt % to about 50 wt %, based on weight of the composition; and   vitamin E in an amount ranging from about 0.5 wt % to about 2 wt %, based on weight of the composition.   
     
     
         31 .- 33 . (canceled) 
     
     
         34 . The composition of  claim 1 , wherein the composition is pharmaceutically acceptable. 
     
     
         35 . A method of treating a subject afflicted with an eye condition, the method comprising:
 administering a composition to an eye of a subject in need thereof, wherein the composition comprises an effective amount of an active pharmaceutical ingredient capable of treating the eye condition, the composition comprising:   an active pharmaceutical ingredient;   a high viscosity liquid carrier material (HVLCM);   a first hydrophobic solvent; and   a hydrophilic solvent.   
     
     
         36 . (canceled) 
     
     
         37 . The method of  claim 35 , wherein the eye condition comprises uveitis, diabetic macular edema, or wet age-related macular degeneration. 
     
     
         38 . The method of  claim 35 , wherein the administering comprises injecting. 
     
     
         39 . The composition of  claim 1 , wherein the benzyl benzoate is present in an amount ranging from about 40 wt % to about 50 wt %, based on weight of the composition. 
     
     
         40 . The composition of  claim 1 , wherein the ethanol is present in an amount ranging from about 3 wt % to about 10 wt %, based on weight of the composition. 
     
     
         41 . The composition of  claim 1 , wherein a weight ratio of SAIB to vitamin E ranges from about 60:1 to about 1:2. 
     
     
         42 . The composition of  claim 1 , wherein a weight ratio of SAIB to vitamin E ranges from about 10:1 to about 1:1.8. 
     
     
         43 . The composition of  claim 1 , wherein a weight ratio of SAIB to vitamin E ranges from about 5:1 to about 1:1.5. 
     
     
         44 . The composition of  claim 1 , wherein a weight ratio of SAIB to vitamin E ranges from about 2:1 to about 1:1.5. 
     
     
         45 . The composition of  claim 1 , wherein the composition has a density at 25° C. and 1 atmosphere ranging from 1.02 g/mL to 1.15 g/mL. 
     
     
         46 . The composition of  claim 1 , wherein the composition has a viscosity ranging from about 1 cP to about 150 cP at 25° C. and 1 atmosphere. 
     
     
         47 . The composition of  claim 1 , wherein the vitamin E is present in an amount ranging from about 0.02 wt % to about 0.09 wt %, based on weight of the composition.