Short duration depot formulations
Methods and compositions for systemically or locally administering by implantation a beneficial agent to a subject are described, and include, for example, depot gel compositions that can be injected into a desired location and which can provide controlled release of a beneficial agent over a short duration of time. The compositions include a low molecular weight biocompatible polymer, a biocompatible solvent having low water miscibility that forms a viscous gel with the polymer and limits water uptake by the implant, and a beneficial agent.
1. A composition comprising:
a polyorthoester having a weight average molecular weight ranging from 3000 to 10,000;
a solvent comprising triacetin and at least one of dimethyl sulfoxide and N-methyl-2-pyrrolidone; and
bupivacaine base or pharmaceutically acceptable salt thereof in an amount ranging from 1 wt % to 20 wt % of the composition,
wherein the weight ratio of polyorthoester to solvent ranges from 40:60 to 75:25.
2. The composition of claim 1 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof consists of bupivacaine base.
3. The composition of claim 1 , wherein the polyorthoester has a weight average molecular weight ranging from 4000 to 8000.
4. The composition of claim 2 , wherein the polyorthoester has a weight average molecular weight ranging from 4000 to 8000.
5. The composition of claim 1 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof is present in an amount ranging from 2 wt % to 20 wt % of the composition.
6. The composition of claim 2 , wherein the bupivacaine base is present in an amount ranging from 2 wt % to 20 wt % of the composition.
7. The composition of claim 3 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof is present in an amount ranging from 2 wt % to 20 wt % of the composition.
8. The composition of claim 4 , wherein the bupivacaine base is present in an amount ranging from 2 wt % to 20 wt % of the composition.
9. The composition of claim 1 , wherein the weight ratio of polyorthoester to solvent ranges from 50:50 to 75:25.
10. The composition of claim 2 , wherein the weight ratio of polyorthoester to solvent ranges from 50:50 to 75:25.
11. The composition of claim 3 , wherein the weight ratio of polyorthoester to solvent ranges from 50:50 to 75:25.
12. The composition of claim 4 , wherein the weight ratio of polyorthoester to solvent ranges from 50:50 to 75:25.
13. The composition of claim 5 , wherein the weight ratio of polyorthoester to solvent ranges from 50:50 to 75:25.
14. The composition of claim 6 , wherein the weight ratio of polyorthoester to solvent ranges from 50:50 to 75:25.
15. The composition of claim 7 , wherein the weight ratio of polyorthoester to solvent ranges from 50:50 to 75:25.
16. The composition of claim 8 , wherein the weight ratio of polyorthoester to solvent ranges from 50:50 to 75:25.
17. A composition comprising:
bupivacaine base or pharmaceutically acceptable salt thereof in an amount ranging from 1 wt % to 20 wt % of the composition; and
a viscous gel comprising:
40 wt % to 70 wt %, based on weight of the viscous gel, of a polyorthoester having a weight average molecular weight ranging from 3000 to 10,000, and
30 wt % to 60 wt %, based on weight of the viscous gel, of a solvent comprising triacetin and at least one of dimethyl sulfoxide and N-methyl-2-pyrrolidone.
18. The composition of claim 17 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof consists of bupivacaine base.
19. The composition of claim 17 , wherein the polyorthoester has a weight average molecular weight ranging from 4000 to 8000.
20. The composition of claim 18 , wherein the polyorthoester has a weight average molecular weight ranging from 4000 to 8000.
21. The composition of claim 17 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof is present in an amount ranging from 2 wt % to 20 wt % of the composition.
22. The composition of claim 18 , wherein the bupivacaine base is present in an amount ranging from 2 wt % to 20 wt % of the composition.
23. The composition of claim 19 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof is present in an amount ranging from 2 wt % to 20 wt % of the composition.
24. The composition of claim 20 , wherein the bupivacaine base is present in an amount ranging from 2 wt % to 20 wt % of the composition.
25. The composition of claim 17 , wherein the polyorthoester is present in an amount ranging from 40 wt % to 65 wt %, based on weight of the viscous gel.
26. The composition of claim 18 , wherein the polyorthoester is present in an amount ranging from 40 wt % to 65 wt %, based on weight of the viscous gel.
27. The composition of claim 19 , wherein the polyorthoester is present in an amount ranging from 40 wt % to 65 wt %, based on weight of the viscous gel.
28. The composition of claim 20 , wherein the polyorthoester is present in an amount ranging from 40 wt % to 65 wt %, based on weight of the viscous gel.
29. The composition of claim 21 , wherein the polyorthoester is present in an amount ranging from 40 wt % to 65 wt %, based on weight of the viscous gel.
30. The composition of claim 22 , wherein the polyorthoester is present in an amount ranging from 40 wt % to 65 wt %, based on weight of the viscous gel.