Depot formulations
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 from about 0.1 wt % to about 5 wt %, based on weight of the composition wherein when the composition is administered intra-ocularly as a single dose to a rabbit, a median amount of sirolimus released from the composition at 6 months after administration ranges from 30% to 100% of a total amount of the sirolimus in the composition at the time of administration.
2. 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.
3. 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.
4. 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.
5. The composition of claim 4 , wherein the PEG is present in an amount ranging from about 40 wt % to about 50 wt %, based on weight of the composition.
6. 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.
7. The composition of claim 1 , wherein the composition has a weight ratio of SAIB: vitamin E ranging from about 0.5 to about 10.
8. 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.
9. 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.
10. The composition of claim 1 , wherein the composition is pharmaceutically acceptable.