Stable pharmaceutical formulations of methylnaltrexone
Stable pharmaceutical compositions useful for administering methylnaltrexone are described, as are methods for making the same. Kits, including these pharmaceutical compositions, also are provided.
1. A stable pharmaceutical preparation comprising a solution of methylnaltrexone or salt thereof and a chelating agent consisting of EDTA, or a derivative thereof, wherein the solution has a pH ranging from about 3.0 to 4.0.
2. The pharmaceutical preparation of claim 1 , wherein less than 1% methylnaltrexone degradation products form following 12 months stored at about room temperature, relative to the total methylnaltrexone present in the solution.
3. The pharmaceutical preparation of claim 1 , wherein less than 1% methylnaltrexone degradation products form following 24 months stored at about room temperature, relative to the total methylnaltrexone present in the solution.
4. The pharmaceutical preparation of claim 3 , wherein the concentration of methylnaltrexone or salt thereof ranges from 0.01 to 100 mg/ml.
5. The pharmaceutical preparation of claim 4 , wherein the concentration of methylnaltrexone or salt thereof ranges from 1.0 to 50.0 mg/ml.
6. The pharmaceutical preparation of claim 5 , wherein the concentration of methylnaltrexone or salt thereof is about 20 mg/ml.
7. The pharmaceutical preparation of claim 5 , wherein the chelating agent consists of dipotassium edetate, disodium edetate, edetate calcium disodium, sodium edetate, trisodium edetate, potassium edetate, or a combination thereof.
8. The pharmaceutical preparation of claim 7 , wherein the chelating agent consists of edetate calcium disodium.
9. The pharmaceutical preparation of claim 8 , wherein the chelating agent concentration ranges from about 0.001 to about 100 mg/ml.
10. The pharmaceutical preparation of claim 9 , wherein the chelating agent concentration ranges from about 0.1 to about 25.0 mg/ml.
11. The pharmaceutical preparation of claim 10 , wherein the chelating agent concentration is about 0.1 to about 2.5 mg/ml.
12. The pharmaceutical preparation of claim 5 , further comprising an isotonicity agent.
13. The pharmaceutical preparation of claim 7 , further comprising an isotonicity agent.
14. The pharmaceutical preparation of claim 8 , further comprising an isotonicity agent.
15. The pharmaceutical preparation of claim 5 , wherein the preparation comprises a buffering agent.
16. The pharmaceutical preparation of claim 7 , wherein the preparation comprises a buffering agent.
17. The pharmaceutical preparation of claim 8 , wherein the preparation comprises a buffering agent.
18. The pharmaceutical preparation of claim 7 , further comprising a preservative and an isotonicity agent.
19. The pharmaceutical preparation of claim 18 , wherein the preparation comprises a buffering agent.
20. The pharmaceutical preparation of claim 1 , wherein the preparation comprises a solution of methylnaltrexone bromide.
21. The pharmaceutical preparation of claim 1 , wherein less than 2% methylnaltrexone degradation products form following 12 months stored at about room temperature, relative to the total methylnaltrexone present in the solution.
22. The pharmaceutical preparation of claim 1 , wherein the preparation is processed under at least one sterilization technique.
23. The pharmaceutical preparation of claim 1 , wherein the solution has a pH from about 3.0 to about 3.5.
24. The pharmaceutical preparation of claim 1 , wherein the solution has a pH of about 3.5.
25. A stable pharmaceutical preparation comprising a solution of methylnaltrexone or salt thereof, EDTA or a derivative thereof, wherein the solution has a pH from about 3.0 to 4.0, and wherein the methylnaltrexone or salt thereof is the sole pharmaceutical active agent.
26. The stable pharmaceutical preparation of claim 25 , wherein the solution has a pH ranging from about 3 to about 3.5.
27. The stable pharmaceutical preparation of claim 26 , wherein the solution has a pH of about 3.5.
28. The pharmaceutical preparation of claim 25 , wherein the pharmaceutical preparation is stable to storage for 3 months at about room temperature.
29. The pharmaceutical preparation of claim 26 , wherein the pharmaceutical preparation is stable to storage for 6 months at about room temperature.
30. The pharmaceutical preparation of claim 26 , wherein the pharmaceutical preparation is stable to storage for 12 months at about room temperature.
31. The pharmaceutical preparation of claim 26 , wherein the pharmaceutical preparation is stable to storage for 24 months at about room temperature.
32. The pharmaceutical preparation of claim 26 , wherein the concentration of methylnaltrexone or salt thereof is about 20 mg/ml.
33. The pharmaceutical preparation of claim 32 , wherein the concentration of EDTA or derivative thereof ranges from about 0.3 to about 0.5 mg/ml.
34. The pharmaceutical preparation of claim 25 , wherein about 1% or less methylnaltrexone degradation products form following 3 months stored at about room temperature, relative to the total methylnaltrexone present in the solution.
35. The pharmaceutical preparation of claim 27 , wherein about 1% or less methylnaltrexone degradation products form following 6 months stored at about room temperature, relative to the total methylnaltrexone present in the solution.
36. The pharmaceutical preparation of claim 27 , wherein about 1% or less methylnaltrexone degradation products form following 12 months stored at about room temperature, relative to the total methylnaltrexone present in the solution.
37. The pharmaceutical preparation of claim 27 , wherein about 1% or less methylnaltrexone degradation products form following 24 months stored at about room temperature, relative to the total methylnaltrexone present in the solution.
38. The stable pharmaceutical preparation of claim 25 , wherein the methylnaltrexone or salt thereof is methylnaltrexone bromide and is at a concentration of about 20 mg/mL, wherein the EDTA or a derivative thereof is at a concentration of about 0.3 to about 0.5 mg/ml, wherein the solution has a pH of about 3.5.
39. The stable pharmaceutical preparation of claim 38 , wherein about 1% or less methylnaltrexone degradation products form following 3 months stored at about room temperature, relative to the total methylnaltrexone present in the solution.