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:
oxycodone or a pharmaceutically acceptable salt thereof present in an amount ranging from 10 to 150 mg;
naloxone or a pharmaceutically acceptable salt thereof; and
a diffusion matrix containing the oxycodone or pharmaceutically acceptable salt thereof and the naloxone or pharmaceutically acceptable salt thereof and comprising:
ethylcellulose present in 1-15% by weight of the total formulation; and
at least one fatty alcohol present in 10-25% by weight of the total formulation;
wherein the matrix is configured to provide sustained, invariant, and independent release of the oxycodone or pharmaceutically acceptable salt thereof and the naloxone or pharmaceutically acceptable salt thereof;
wherein the oxycodone or pharmaceutically acceptable salt thereof and the naloxone or pharmaceutically acceptable salt thereof are present in a weight ratio of 2:1.
2. The pharmaceutical formulation of claim 1 , wherein the oxycodone is present as oxycodone hydrochloride.
3. The pharmaceutical formulation of claim 2 , wherein the naloxone is present as naloxone hydrochloride.
4. The pharmaceutical formulation of claim 1 , wherein the naloxone is present as naloxone hydrochloride.
5. The pharmaceutical formulation of claim 1 , wherein the oxycodone or pharmaceutically acceptable salt thereof is present in an amount ranging from 10 to 80 mg.
6. The pharmaceutical formulation of claim 5 , wherein the oxycodone or pharmaceutically acceptable salt thereof is present in an amount ranging from 10 to 40 mg.
7. The pharmaceutical formulation of claim 6 , wherein the oxycodone or pharmaceutically acceptable salt thereof is present in an amount ranging from 10 to 30 mg.
8. The pharmaceutical formulation of claim 1 , wherein the ethylcellulose is present in 3-12% by weight of the total formulation.
9. The pharmaceutical formulation of claim 8 , wherein the ethylcellulose is present in 5-9% by weight of the total formulation.
10. The pharmaceutical formulation of claim 1 , wherein the fatty alcohol is present in 15-20% by weight of the total formulation.
11. The pharmaceutical formulation of claim 1 , wherein the fatty alcohol is selected from lauryl alcohol, myristyl alcohol, stearyl alcohol, cetylstearyl alcohol, ceryl alcohol, and cetyl alcohol.
12. The pharmaceutical formulation of claim 11 , wherein the fatty alcohol is stearyl alcohol.
13. The pharmaceutical formulation of claim 5 , wherein the fatty alcohol is stearyl alcohol.
14. The pharmaceutical formulation of claim 6 , wherein the fatty alcohol is stearyl alcohol.
15. The pharmaceutical formulation of claim 1 , wherein the matrix is further configured to provide equal percentage release per time unit of the oxycodone or pharmaceutically acceptable salt thereof and the naloxone or pharmaceutically acceptable salt thereof.
16. The pharmaceutical formulation of claim 15 , wherein the equal percentage release per time unit of the oxycodone or pharmaceutically acceptable salt thereof and the naloxone or pharmaceutically acceptable salt thereof includes no more than 20% deviation from the mean release value for the oxycodone or pharmaceutically acceptable salt thereof or the naloxone or pharmaceutically acceptable salt thereof.
17. The pharmaceutical formulation of claim 1 , wherein the matrix is not based on a polymethacrylate.
18. The pharmaceutical formulation of claim 1 , wherein the matrix does not comprise a relevant amount of a hydroxyalkylcellulose.
19. The pharmaceutical formulation of claim 1 , wherein the sustained, invariant, and independent release characteristics of the matrix are determined by the ethyl cellulose and the at least one fatty alcohol.
20. The pharmaceutical formulation of claim 1 , wherein the formulation is in the form of a tablet.