Matrix for sustained, invariant and independent release of active compounds

Abstract

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 - 40 . (canceled) 
     
     
         41 . An oral pharmaceutical formulation comprising a diffusion matrix that comprises:
 oxycodone or a pharmaceutically acceptable salt thereof;   naloxone or a pharmaceutically acceptable salt thereof; and   ethylcellulose in an amount of 1-15% by weight of the total formulation or one or more fatty alcohols in an amount of 5-30% by weight of the total formulation.   
     
     
         42 . The pharmaceutical formulation of  claim 41 , wherein the naloxone is present in the form of a pharmaceutically acceptable salt thereof. 
     
     
         43 . The pharmaceutical formulation of  claim 41 , wherein the naloxone is present in the form of naloxone hydrochloride. 
     
     
         44 . The pharmaceutical formulation of  claim 41 , wherein the naloxone or pharmaceutically acceptable salt thereof is present in an amount ranging from 1 to 50 mg. 
     
     
         45 . The pharmaceutical formulation of  claim 41 , wherein the naloxone or pharmaceutically acceptable salt thereof is present in an amount ranging from 1 to 40 mg. 
     
     
         46 . The pharmaceutical formulation of  claim 41 , wherein the naloxone or pharmaceutically acceptable salt thereof is present in an amount ranging from 1 to 20 mg. 
     
     
         47 . The pharmaceutical formulation of  claim 41 , wherein the naloxone or pharmaceutically acceptable salt thereof is present in an amount ranging from 1 to 10 mg. 
     
     
         48 . The pharmaceutical formulation of  claim 41 , wherein the naloxone or pharmaceutically acceptable salt thereof is present in an amount ranging from 5 to 20 mg. 
     
     
         49 . The pharmaceutical formulation of  claim 41 , wherein the oxycodone is present in the form of a pharmaceutically acceptable salt thereof. 
     
     
         50 . The pharmaceutical formulation of  claim 41 , wherein the oxycodone is present in the form of oxycodone hydrochloride. 
     
     
         51 . The pharmaceutical formulation of  claim 41 , wherein the oxycodone or pharmaceutically acceptable salt thereof is present in an amount ranging from 10 to 150 mg. 
     
     
         52 . The pharmaceutical formulation of  claim 41 , wherein the oxycodone or pharmaceutically acceptable salt thereof is present in an amount ranging from 10 to 80 mg. 
     
     
         53 . The pharmaceutical formulation of  claim 41 , wherein the oxycodone or pharmaceutically acceptable salt thereof is present in an amount ranging from 10 to 40 mg. 
     
     
         54 . The pharmaceutical formulation of  claim 41 , wherein the oxycodone or pharmaceutically acceptable salt thereof is present in an amount ranging from 10 to 30 mg. 
     
     
         55 . The pharmaceutical formulation of  claim 41 , wherein the oxycodone or pharmaceutically acceptable salt thereof is present in an amount ranging from 5 to 50 mg. 
     
     
         56 . The pharmaceutical formulation of  claim 41 , wherein the oxycodone or pharmaceutically acceptable salt thereof and the naloxone or pharmaceutically acceptable salt thereof are present in a weight ratio ranging from 25:1 to 1:1. 
     
     
         57 . The pharmaceutical formulation of  claim 41 , wherein the oxycodone or pharmaceutically acceptable salt thereof and the naloxone or pharmaceutically acceptable salt thereof are present in a weight ratio ranging from 5:1 to 1:1. 
     
     
         58 . The pharmaceutical formulation of  claim 41 , wherein the oxycodone or pharmaceutically acceptable salt thereof and the naloxone or pharmaceutically acceptable salt thereof are present in a weight ratio of 5:1, 4:1, 3:1, 2:1, or 1:1. 
     
     
         59 . The pharmaceutical formulation of  claim 41 , 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. 
     
     
         60 . The pharmaceutical formulation of  claim 41 , wherein the diffusion matrix comprises ethylcellulose. 
     
     
         61 . The pharmaceutical formulation of  claim 41 , wherein the diffusion matrix comprises ethylcellulose and not one or more fatty alcohols. 
     
     
         62 . The pharmaceutical formulation of  claim 41 , wherein the diffusion matrix comprises ethylcellulose in an amount of 3-12% by weight of the total formulation. 
     
     
         63 . The pharmaceutical formulation of  claim 41 , wherein the diffusion matrix comprises ethylcellulose in an amount of 5-9% by weight of the total formulation. 
     
     
         64 . The pharmaceutical formulation of  claim 41 , wherein the diffusion matrix comprises ethylcellulose in an amount of 6-8% by weight of the total formulation. 
     
     
         65 . The pharmaceutical formulation of  claim 41 , wherein the diffusion matrix comprises one or more fatty alcohols. 
     
     
         66 . The pharmaceutical formulation of  claim 41 , wherein the diffusion matrix comprises one or more fatty alcohols and not ethylcellulose. 
     
     
         67 . The pharmaceutical formulation of  claim 41 , wherein the diffusion matrix comprises one or more fatty alcohols in an amount of 10-25% by weight of the total formulation. 
     
     
         68 . The pharmaceutical formulation of  claim 41 , wherein the diffusion matrix comprises one or more fatty alcohols in an amount of 15-20% by weight of the total formulation. 
     
     
         69 . The pharmaceutical formulation of  claim 41 , wherein the diffusion matrix comprises one or more fatty alcohols selected from lauryl alcohol, myristyl alcohol, stearyl alcohol, cetylstearyl alcohol, ceryl alcohol, and cetyl alcohol. 
     
     
         70 . The pharmaceutical formulation of  claim 41 , wherein the diffusion matrix comprises stearyl alcohol. 
     
     
         71 . The pharmaceutical formulation of  claim 41 , wherein the formulation is in the form of a tablet. 
     
     
         72 . The pharmaceutical formulation of  claim 41 , wherein the formulation releases 10% to 30% of the oxycodone (or pharmaceutically acceptable salt thereof) or the naloxone (or pharmaceutically acceptable salt thereof) after 15 minutes. 
     
     
         73 . The pharmaceutical formulation of  claim 41 , wherein the formulation releases 40% to 85% of the oxycodone (or pharmaceutically acceptable salt thereof) or the naloxone (or pharmaceutically acceptable salt thereof) after 2 hours. 
     
     
         74 . The pharmaceutical formulation of  claim 41 , wherein the formulation releases 60% to 100% of the oxycodone (or pharmaceutically acceptable salt thereof) or the naloxone (or pharmaceutically acceptable salt thereof) after 7 hours. 
     
     
         75 . The pharmaceutical formulation of  claim 41 , wherein the formulation releases 85% to 100% of the oxycodone (or pharmaceutically acceptable salt thereof) or the naloxone (or pharmaceutically acceptable salt thereof) after 12 hours. 
     
     
         76 . The pharmaceutical formulation of  claim 41 , wherein the diffusion matrix is a sustained release matrix. 
     
     
         77 . The pharmaceutical formulation of  claim 41 , wherein the diffusion matrix further comprises stearate or stearic acid. 
     
     
         78 . The pharmaceutical formulation of  claim 41 , wherein the diffusion matrix further comprises triacetin. 
     
     
         79 . The pharmaceutical formulation of  claim 41 , wherein the diffusion matrix further comprises talcum. 
     
     
         80 . An oral pharmaceutical formulation comprising a diffusion matrix that comprises:
 10 to 30 mg oxycodone or a pharmaceutically acceptable salt thereof;   naloxone or a pharmaceutically acceptable salt thereof; and   ethylcellulose in an amount of 1-15% by weight of the total formulation or one or more fatty alcohols in an amount of 5-30% by weight of the total formulation;   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;   wherein the formulation releases 60% to 100% of the oxycodone (or pharmaceutically acceptable salt thereof) or the naloxone (or pharmaceutically acceptable salt thereof) after 7 hours.   
     
     
         81 . An oral pharmaceutical formulation comprising a diffusion matrix that comprises:
 oxycodone or a pharmaceutically acceptable salt thereof;   1 to 10 mg naloxone or a pharmaceutically acceptable salt thereof; and   ethylcellulose in an amount of 1-15% by weight of the total formulation or one or more fatty alcohols in an amount of 5-30% by weight of the total formulation;   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;   wherein the formulation releases 60% to 100% of the oxycodone (or pharmaceutically acceptable salt thereof) or the naloxone (or pharmaceutically acceptable salt thereof) after 7 hours.