Pharmaceutical preparation containing oxycodone and naloxone

Abstract

The invention concerns a storage stable pharmaceutical preparation comprising oxycodone and naloxone for use in pain therapy with the active compounds being released from the preparation in a sustained, invariant and independent manner.

1 . A storage stable pharmaceutical preparation comprising oxycodone and naloxone in a substantially non-swellable diffusion matrix comprising ethyl cellulose, characterized in that the active compounds are released from the preparation in a sustained, invariant and independent manner.  
     
     
         2 . Preparation according to  claim 1 , characterized in that oxycodone and/or naloxone are present in the form of pharmaceutically acceptable and equally active derivatives such as the free base, salts and the like.  
     
     
         3 . Preparation according to  claim 2 , characterized in that oxycodone and/or naloxone are present as their hydrochloride, sulfate, bisulfate, tatrate, nitrate, citrate, bitatrate, phosphate, malate, maleate, hydrobromide, hydroiodide, fumarate or succinate.  
     
     
         4 . Preparation according to  claim 3 , characterized in that oxycodone is present in excess referred to the unit dosage amount of naloxone.  
     
     
         5 . Preparation according to  claim 1 , characterized in that naloxone is present in an amount range of about 1 g to about 50 mg.  
     
     
         6 . Preparation according to  claim 1 , characterized in that oxycodone is present in an amount range of about 10 mg to about 150 mg.  
     
     
         7 . Preparation according to  claim 1 , characterized in that oxycodone and naloxone are present in weight ratio ranges of from about 25:1 to about 1:1.  
     
     
         8 . Preparation according to  claim 7 , characterized in that the preparation comprises a substantially non-erosive diffusion matrix.  
     
     
         9 . Preparation according to  claim 8 , characterized in that the diffusion matrix comprises at least ethylcellulose and at least one fatty alcohol as the components that essentially influence the release behavior of the active compounds.  
     
     
         10 . Preparation according to  claim 9 , characterized in that the preparation does not comprise relevant parts of alkaline and/or water-swellable substance.  
     
     
         11 . Preparation according to  claim 10 , characterized in that the preparation contains fillers and additional substances.  
     
     
         12 . Preparation according to  claim 11 , characterized in that it comprises magnesium stearate, calcium stearate and/or calcium laureate and/or fatty acids.  
     
     
         13 . Preparation according to  claim 11 , characterized in that it comprises a flowing agent selected from the group consisting of highly-disperse silica, talcum, corn starch, magnesium oxide and magnesium and calcium stearate.  
     
     
         14 . A storage stable pharmaceutical preparation comprising oxycodone and naloxone in a substantially non-swellable diffusion matrix, characterized in that the matrix is influenced with respect to its substantial release characteristics by ethylcellulose and at lease one fatty alcohol and that the preparation comprises oxycodone and naloxone in a weight ratio of from about 25:1 to about 1:1.  
     
     
         15 . Preparation according to  claim 14 , characterized in that the oxycodone and naloxone are present in the form of pharmaceutically acceptable and equally active derivatives.  
     
     
         16 . Preparation according to  claim 15 , characterized in that oxycodone and naloxone are present as hydrochloride, sulfate, bisulfate, tatrate, nitrate, citrate, bitatrate, phosphate, malate, maleate, hydrobromide, hydroiodide, fumarate or succinate.  
     
     
         17 . Preparation according to  claim 16 , characterized in that oxycodone is present in excess referred to the unit dosage amount of naloxone.  
     
     
         18 . Preparation according to  claim 17 , characterized in that oxycodone is present in an amount range of about 1 mg to about 50 mg.  
     
     
         19 . Preparation according to  claim 18 , characterized in that oxycodone is present in an amount range of about 10 mg to about 150 mg.  
     
     
         20 . Preparation according to  claim 19 , characterized in that preparation comprises a substantially non-swellable and non-erosive diffusion matrix.  
     
     
         21 . Preparation according to  claim 20 , characterized in that the diffusion matrix comprises at least ethylcellulose and at least one fatty alcohol as the components that essentially influence the release behavior of the active compounds.  
     
     
         22 . Preparation according to  claim 21 , characterized in that the preparation does not comprise relevant parts of alkaline and/or water-swellable substance.  
     
     
         23 . Preparation according to  claim 22 , characterized in that the fatty alcohols comprise lauryl, myrestyl, stearyl, cetostearyl, ceryl and/or cetyl alcohol.  
     
     
         24 . Preparation according to  claim 23 , characterized in that the preparation comprises fillers and additional substances.  
     
     
         25 . Preparation according to  claim 24 , characterized in that it comprises magnesium stearate, calcium stearate and/or calcium laureate and/or fatty acids.  
     
     
         26 . Preparation according to  claim 24 , characterized in that it comprises a flowing agent selected from the group consisting of highly-disperse silica, talcum, corn starch, magnesium oxide, magnesium stearate and calcium stearate.  
     
     
         27 . Preparation according to  claim 26 , characterized in that commercially available polymer mixtures which comprise ethylcellulose are used instead of ethylcellulose.  
     
     
         28 . Preparation according to  claim 27 , characterized in that the preparation has been formulated for oral, nasal, rectal application or for application by inhalation.  
     
     
         29 . Preparation according to  claim 28 , characterized in that the preparation is in the form of a tablet, pill, capsule, granule or powder.  
     
     
         30 . Preparation according to  claim 29 , characterized in that preparation or precursors thereof are produced by build-up and/or break-down granulation.  
     
     
         31 . Preparation according to  claim 29 , characterized in that the preparation or precursors thereof are produced by extrusion.  
     
     
         32 . Preparation according to  claim 31 , characterized in that the preparation can be stored over a period of at least 2 years under standard conditions (60% relatively humidity, 25° C.) in accordance with admission guidelines.  
     
     
         33 . A preparation according to  claim 6 , characterized in that oxycodone is present in an amount range of from about 10 mg to about 80 mg.  
     
     
         34 . A preparation according to  claim 7 , characterized in that oxycodone and naloxone are present in weight ratio ranges of from about 5:1 to about 1:1.  
     
     
         35 . A preparation according to  claim 10 , characterized in that the preparation does not comprise relevant parts of derivatives of acrylic acid and/or hydroxy alkyl celluloses.  
     
     
         36 . A preparation according to  claim 11 , further comprising one or more materials from the group consisting of lubricants, flowing agents, plasticizers and the like.  
     
     
         37 . A preparation according to  claim 12 , characterized in that it comprises stearic acid.  
     
     
         38 . A storage stable pharmaceutical preparation according to  claim 14 , comprising oxycodone and naloxone in a substantially non-swellable diffusion matrix, characterized in that the matrix is influenced with respect to its substantial release characteristics by ethylcellulose and at lease one fatty alcohol and that the preparation comprises oxycodone and naloxone in a weight ratio of from about 5:1 to about 1:1.  
     
     
         39 . A preparation according to  claim 19 , characterized in that oxycodone is present in an amount range of about 10 mg to about 80 mg.  
     
     
         40 . A preparation according to  claim 22 , characterized in that the preparation does not comprise relevant parts of derivatives of acrylic acid and/or hydroxy alkyl celluloses.  
     
     
         41 . A preparation according to  claim 24 , further comprising one or more materials from the group consisting of lubricants, flowing agents, plasticizers and the like.  
     
     
         42 . A preparation according to  claim 25 , characterized in that it comprises stearic acid.  
     
     
         43 . A preparation according to  claim 27 , characterized in that the commercially available polymer mixture is Surelease® E-7-7050.  
     
     
         44 . A preparation according to  claim 15 , characterized in that the pharmaceutically acceptable and equally active derivatives are the free-base, salts and the like.