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 method of administering bupivacaine base or pharmaceutically acceptable salt thereof, comprising administering to a subject a composition comprising:
a polyorthoester having a weight average molecular weight ranging from 3000 to 10,000;
triacetin; 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 triacetin ranges from 40:60 to 75:25.
2. The method of claim 1 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof consists of bupivacaine base.
3. The method of claim 1 , wherein the polyorthoester has a weight average molecular weight ranging from 4000 to 8000.
4. The method of claim 2 , wherein the polyorthoester has a weight average molecular weight ranging from 4000 to 8000.
5. The method 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 method of claim 2 , wherein the bupivacaine base is present in an amount ranging from 2 wt % to 20 wt % of the composition.
7. The method 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 method of claim 4 , wherein the bupivacaine base is present in an amount ranging from 2 wt % to 20 wt % of the composition.
9. The method of claim 1 , wherein the weight ratio of polyorthoester to triacetin ranges from 50:50 to 75:25.
10. The method of claim 2 , wherein the weight ratio of polyorthoester to triacetin ranges from 50:50 to 75:25.
11. The method of claim 3 , wherein the weight ratio of polyorthoester to triacetin ranges from 50:50 to 75:25.
12. The method of claim 4 , wherein the weight ratio of polyorthoester to triacetin ranges from 50:50 to 75:25.
13. The method of claim 5 , wherein the weight ratio of polyorthoester to triacetin ranges from 50:50 to 75:25.
14. The method of claim 6 , wherein the weight ratio of polyorthoester to triacetin ranges from 50:50 to 75:25.
15. The method of claim 7 , wherein the weight ratio of polyorthoester to triacetin ranges from 50:50 to 75:25.
16. The method of claim 8 , wherein the weight ratio of polyorthoester to triacetin ranges from 50:50 to 75:25.
17. The method of claim 1 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof is released from the composition in a controlled manner over a duration equal to or less than two weeks.
18. The method of claim 1 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof is released from the composition in a controlled manner over a duration ranging from 24 hours to 2 weeks.
19. The method of claim 1 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof is released from the composition in a controlled manner over a duration ranging from 24 hours to 10 days.
20. The method of claim 1 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof is released from the composition in a controlled manner over a duration ranging from 24 hours to 7 days.
21. The method of claim 1 , wherein the administering comprises locally administering.
22. A method of administering bupivacaine base or pharmaceutically acceptable salt thereof, comprising administering to a subject 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.
23. The method of claim 22 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof comprises bupivacaine base.
24. The method of claim 22 , wherein the polyorthoester has a weight average molecular weight ranging from 4000 to 8000.
25. The method of claim 23 , wherein the polyorthoester has a weight average molecular weight ranging from 4000 to 8000.
26. The method of claim 22 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof is present in an amount ranging from 2 wt % to 20 wt % of the composition.
27. The method of claim 23 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof is present in an amount ranging from 2 wt % to 20 wt % of the composition.
28. The method of claim 24 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof is present in an amount ranging from 2 wt % to 20 wt % of the composition.
29. The method of claim 25 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof is present in an amount ranging from 2 wt % to 20 wt % of the composition.
30. The method of claim 22 , wherein the weight ratio of polyorthoester to solvent ranges from 50:50 to 75:25.
31. The method of claim 23 , wherein the weight ratio of polyorthoester to solvent ranges from 50:50 to 75:25.
32. The method of claim 24 , wherein the weight ratio of polyorthoester to solvent ranges from 50:50 to 75:25.
33. The method of claim 25 , wherein the weight ratio of polyorthoester to solvent ranges from 50:50 to 75:25.
34. The method of claim 26 , wherein the weight ratio of polyorthoester to solvent ranges from 50:50 to 75:25.
35. The method of claim 27 , wherein the weight ratio of polyorthoester to solvent ranges from 50:50 to 75:25.
36. The method of claim 28 , wherein the weight ratio of polyorthoester to solvent ranges from 50:50 to 75:25.
37. The method of claim 29 , wherein the weight ratio of polyorthoester to solvent ranges from 50:50 to 75:25.
38. The method of claim 22 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof is released from the composition in a controlled manner over a duration equal to or less than two weeks.
39. The method of claim 22 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof is released from the composition in a controlled manner over a duration ranging from 24 hours to 2 weeks.
40. The method of claim 22 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof is released from the composition in a controlled manner over a duration ranging from 24 hours to 10 days.
41. The method of claim 22 , wherein the bupivacaine base or pharmaceutically acceptable salt thereof is released from the composition in a controlled manner over a duration ranging from 24 hours to 7 days.
42. The method of claim 22 , wherein the administering comprises locally administering.