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 10 wt %, based on weight of the composition;   sucrose acetate isobutyrate (SAIB) present in an amount ranging from about 0.1 wt % to about 10 wt %, based on weight of the composition;   benzyl benzoate present in an amount ranging from about 30 wt % to about 60 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 30 wt % to about 60 wt %, based on weight of the composition; and   vitamin E present in an amount ranging up to 5 wt %, based on weight of the composition.   
     
     
         2 - 5 . (canceled) 
     
     
         6 . The composition of  claim 1 , wherein the composition comprises from about 1 wt % to about 5 wt % of the sirolimus, based on weight of the composition. 
     
     
         7 - 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 - 20 . (canceled) 
     
     
         21 . The composition of  claim 1 , wherein the PEG is present in an amount ranging from about 35 wt % to about 50 wt %, based on weight of the composition. 
     
     
         22 . The composition of  claim 21 , wherein the PEG is present in an amount ranging from about 40 wt % to about 50 wt %, based on weight of the composition. 
     
     
         23 - 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 . (canceled) 
     
     
         29 . The composition of  claim 1 , wherein:
 the sirolimus is present in an amount ranging from about 1 wt % to about 5 wt %, based on weight of the composition;   the benzyl benzoate is present in an amount ranging from about 30 wt % to about 45 wt %, based on weight of the composition;   the PEG is present in an amount ranging from about 40 wt % to about 50 wt %, based on weight of the composition; and   the vitamin E is present in an amount ranging from about 0.5 wt % to about 2 wt %, based on weight of the composition.   
     
     
         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;   SAM 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 - 38 . (canceled) 
     
     
         39 . The composition of  claim 1 , wherein at least 98% of the sirolimus in the composition remains after storage in a 2 mL crimp sealed glass vial for 18 weeks at 5° C./60% RH. 
     
     
         40 . The composition of  claim 6 , wherein at least 98% of the sirolimus in the composition remains after storage in a 2 mL crimp sealed glass vial for 18 weeks at 5° C./60% RH. 
     
     
         41 . The composition of  claim 10 , wherein at least 98% of the sirolimus in the composition remains after storage in a 2 mL crimp sealed glass vial for 18 weeks at 5° C./60% RH. 
     
     
         42 . The composition of  claim 21 , wherein at least 98% of the sirolimus in the composition remains after storage in a 2 mL crimp sealed glass vial for 18 weeks at 5° C./60% RH. 
     
     
         43 . The composition of  claim 22 , wherein at least 98% of the sirolimus in the composition remains after storage in a 2 mL crimp sealed glass vial for 18 weeks at 5° C./60% RH. 
     
     
         44 . The composition of  claim 25 , wherein at least 98% of the sirolimus in the composition remains after storage in a 2 mL crimp sealed glass vial for 18 weeks at 5° C./60% RH. 
     
     
         45 . The composition of  claim 26 , wherein at least 98% of the sirolimus in the composition remains after storage in a 2 mL crimp sealed glass vial for 18 weeks at 5° C./60% RH. 
     
     
         46 . The composition of  claim 27 , wherein at least 98% of the sirolimus in the composition remains after storage in a 2 mL crimp sealed glass vial for 18 weeks at 5° C./60% RH. 
     
     
         47 . The composition of  claim 29 , wherein at least 98% of the sirolimus in the composition remains after storage in a 2 mL crimp sealed glass vial for 18 weeks at 5° C./60% RH. 
     
     
         48 . The composition of  claim 30 , wherein at least 98% of the sirolimus in the composition remains after storage in a 2 mL crimp sealed glass vial for 18 weeks at 5° C./60% RH.