Matrix for sustained, invariant and independent release of active compounds
The invention concerns a storage stable pharmaceutical formulation comprising preferably two active compounds in a non-swellable diffusion matrix, whereby the compounds are released from the matrix in a sustained, invariant and, if several compounds are present, independent manner and the matrix is determined with respect to its substantial release characteristics by ethylcellulose and at least one fatty alcohol. The invention also concerns methods for producing such pharmaceutical formulations.
1. An oral pharmaceutical formulation comprising:
a diffusion matrix that comprises naloxone or a pharmaceutically acceptable salt thereof as the only pharmaceutically active agent in the formulation; and
ethylcellulose in an amount of 1-15% by weight of the total formulation.
2. The pharmaceutical formulation of claim 1 , wherein the naloxone is present in the form of a pharmaceutically acceptable salt thereof.
3. The pharmaceutical formulation of claim 1 , wherein the naloxone is present in the form of naloxone hydrochloride.
4. The pharmaceutical formulation of claim 1 , wherein the naloxone or pharmaceutically acceptable salt thereof is present in an amount ranging from 1 to 50 mg.
5. The pharmaceutical formulation of claim 1 , wherein the naloxone or pharmaceutically acceptable salt thereof is present in an amount ranging from 1 to 40 mg.
6. The pharmaceutical formulation of claim 1 , wherein the naloxone or pharmaceutically acceptable salt thereof is present in an amount ranging from 1 to 30 mg.
7. The pharmaceutical formulation of claim 1 , wherein the naloxone or pharmaceutically acceptable salt thereof is present in an amount ranging from 1 to 20 mg.
8. The pharmaceutical formulation of claim 1 , wherein the naloxone or pharmaceutically acceptable salt thereof is present in an amount ranging from 1 to 10 mg.
9. The pharmaceutical formulation of claim 1 , wherein the naloxone or pharmaceutically acceptable salt thereof is present in an amount ranging from 5 to 30 mg.
10. The pharmaceutical formulation of claim 1 , wherein the naloxone or pharmaceutically acceptable salt thereof is present in an amount ranging from 5 to 20 mg.
11. The pharmaceutical formulation of claim 1 , wherein the ethylcellulose is present in an amount of 3-12% by weight of the total formulation.
12. The pharmaceutical formulation of claim 1 , wherein the ethylcellulose is present in an amount of 5-9% by weight of the total formulation.
13. The pharmaceutical formulation of claim 1 , wherein the ethylcellulose is present in an amount of 6-8% by weight of the total formulation.
14. The pharmaceutical formulation of claim 1 , further comprising at least one fatty alcohol.
15. The pharmaceutical formulation of claim 14 , wherein the fatty alcohol is present in an amount of 5-30% by weight of the total formulation.
16. The pharmaceutical formulation of claim 14 , wherein the fatty alcohol is present in an amount of 10-25% by weight of the total formulation.
17. The pharmaceutical formulation of claim 14 , wherein the fatty alcohol is present in an amount of 15-20% by weight of the total formulation.
18. The pharmaceutical formulation of claim 14 , wherein the fatty alcohol is selected from lauryl alcohol, myristyl alcohol, stearyl alcohol, cetylstearyl alcohol, ceryl alcohol, and cetyl alcohol.
19. The pharmaceutical formulation of claim 14 , wherein the fatty alcohol is stearyl alcohol.
20. The pharmaceutical formulation of claim 1 , wherein the formulation is in the form of a tablet.
21. The pharmaceutical formulation of claim 1 , wherein the formulation releases 30% to 60% of the naloxone or pharmaceutically acceptable salt thereof after 90 minutes.
22. The pharmaceutical formulation of claim 1 , wherein the formulation releases 30% to 70% of the naloxone or pharmaceutically acceptable salt thereof after 120 minutes.
23. The pharmaceutical formulation of claim 1 , wherein the formulation releases 55% to 90% of the naloxone or pharmaceutically acceptable salt thereof after 420 minutes.
24. The pharmaceutical formulation of claim 1 , wherein the formulation releases 60% to 90% of the naloxone or pharmaceutically acceptable salt thereof after 600 minutes.
25. The pharmaceutical formulation of claim 1 , wherein the diffusion matrix is a sustained release matrix.
26. An oral sustained release pharmaceutical formulation comprising:
1 to 40 mg of naloxone or a pharmaceutically acceptable salt thereof as the only pharmaceutically active agent in the formulation; and
a diffusion matrix that comprises ethylcellulose in an amount of 1-15% by weight of the total formulation and that contains and provides invariant release of the naloxone or pharmaceutically acceptable salt thereof;
wherein the matrix releases 55% to 90% of the naloxone or pharmaceutically acceptable salt thereof after 420 minutes.
27. The pharmaceutical formulation of claim 26 , wherein the naloxone or pharmaceutically acceptable salt thereof is present in an amount ranging from 1 to 20 mg.
28. The pharmaceutical formulation of claim 26 , wherein the naloxone or pharmaceutically acceptable salt thereof is present in an amount ranging from 1 to 10 mg.
29. The pharmaceutical formulation of claim 26 , wherein the naloxone or pharmaceutically acceptable salt thereof is present in an amount ranging from 5 to 20 mg.
30. A method of treating an opioid-induced side effect in a subject in need thereof comprising administering to the subject the pharmaceutical formulation of claim 1 .
31. The method of claim 30 , wherein the opioid-induced side effect is selected from dizziness, breath depression, opioid-abuse, development of tolerance and addiction, obstipation, and pruritus.
32. The method of claim 30 , wherein the opioid-induced side effect is obstipation.
33. The method of claim 30 , wherein the subject is being treated with an opioid analgesic.
34. A method of treating an opioid-induced side effect in a subject in need thereof comprising administering to the subject the pharmaceutical formulation of claim 26 .
35. The method of claim 34 , wherein the opioid-induced side effect is selected from dizziness, breath depression, opioid-abuse, development of tolerance and addiction, obstipation, and pruritus.
36. The method of claim 34 , wherein the opioid-induced side effect is obstipation.
37. The method of claim 36 , wherein the subject is being treated with an opioid analgesic.