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 characterized in that the active compounds are released from the preparation in a sustained, invariant and independent manner. 
     
     
         2 . The storage stable pharmaceutical preparation of  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 . The storage stable pharmaceutical preparation of  claim 2 ,
 characterized in that 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 . The storage stable pharmaceutical preparation of  claim 1 ,
 characterized in that oxycodone is present in excess referred to the unit dosage amount of naloxone.   
     
     
         5 . The storage stable pharmaceutical preparation of  claim 1 ,
 characterized in that Naloxone is present in an amount range of 1 to 50 mg.   
     
     
         6 . The storage stable pharmaceutical preparation of  claim 1 ,
 characterized in that oxycodone is present in an amount range of 10 to 150 mg, preferably of 10 to 80 mg.   
     
     
         7 . The storage stable pharmaceutical preparation of  claim 1 ,
 characterized in that oxycodone and naloxone are present in weight ratio ranges of maximal 25:1, preferably of maximal 20:1, 15:1, especially preferably of 5:1, 4:1, 3:1, 2:1 or 1:1.   
     
     
         8 . The storage stable pharmaceutical preparation of  claim 1 ,
 characterized in that the preparation comprises substantially a non-swellable and non-erosive diffusion matrix.   
     
     
         9 . The storage stable pharmaceutical preparation of  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 behaviour of the active compounds.   
     
     
         10 . The storage stable pharmaceutical preparation of  claim 8 ,
 characterized in that the preparation does not comprise relevant parts of alkaline and/or water-swellable substances, especially of derivatives of acrylic acid and/or hydroxyalkyl celluloses.   
     
     
         11 . The storage stable pharmaceutical preparation of  claim 1 ,
 characterized in that the preparation contains usual fillers and additional substances, especially lubricants, flowing agents, plasticizers and the like.   
     
     
         12 . The storage stable pharmaceutical preparation of  claim 11 ,
 characterized in that it comprises magnesium stearate, calcium stearate and/or calcium laureate and/or fatty acids, preferably stearic acid as the lubricant.   
     
     
         13 . The storage stable pharmaceutical preparation of  claim 11 ,
 characterized in that it comprises highly-disperse silica, preferably Aerosil®, Talcum, corn starch, magnesium oxide and magnesium and/or calcium stearate as the flowing agent.   
     
     
         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 least one fatty alcohol and that the preparation comprises oxycodone and naloxone in a weight ratio of maximal 25:1, preferably maximal 20:1, 15:1, especially preferably of 5:1, 4:1, 3:1, 2:1 or 1:1.   
     
     
         15 . The storage stable pharmaceutical preparation of  claim 14 ,
 characterized in that oxycodone and naloxone are present in the form of pharmaceutically acceptable and equally active derivatives, such as the free-base, salts, and the like.   
     
     
         16 . The storage stable pharmaceutical preparation of  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 . The storage stable pharmaceutical preparation of  claim 14 ,
 characterized in that oxycodone is present in excess referred to the unit dosage amount of naloxone.   
     
     
         18 . The storage stable pharmaceutical preparation of  claim 14 ,
 characterized in that naloxone is present in an amount range of 1 to 50 mg.   
     
     
         19 . The storage stable pharmaceutical preparation of  claim 14 ,
 characterized in that oxycodone is present in an amount range of 10 to 150 mg, preferably of 10 to 80 mg.   
     
     
         20 . The storage stable pharmaceutical preparation of  claim 14 ,
 characterized in that the preparation comprises a substantially non-swellable and non-erosive diffusion matrix.   
     
     
         21 . The storage stable pharmaceutical preparation of  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 behaviour of the active compounds.   
     
     
         22 . The storage stable pharmaceutical preparation of  claim 20 ,
 characterized in that the preparation does not comprise relevant parts of alkaline and/or water-swellable substances, especially of derivatives of acrylic acid and/or hydroxy alkyl celluloses.   
     
     
         23 . The storage stable pharmaceutical preparation of  claim 14 ,
 characterized in that the fatty alcohols comprise lauryl, myrestyl, stearyl, cetostearyl, ceryl and/or cetyl alcohol, especially preferably stearyl alcohol.   
     
     
         24 . The storage stable pharmaceutical preparation of  claim 14 ,
 characterized in that the preparation comprises usual fillers and additional substances, especially lubricants, flowing agents, plasticizers and the like.   
     
     
         25 . The storage stable pharmaceutical preparation of  claim 24 ,
 characterized in that it comprises magnesium stearate, calcium stearate and/or calcium laureat and/or fatty acids, preferably stearic acid as lubricant.   
     
     
         26 . The storage stable pharmaceutical preparation of  claim 24 ,
 characterized in that it comprises highly dispersed silica, preferably Aerosil®, talcum, corn starch, magnesium oxide, magnesium stearate and/or calcium stearate as flowing agent.   
     
     
         27 . The storage stable pharmaceutical preparation of  claim 1 ,
 characterized in that commercially available polymer mixtures which comprise ethylcellulose, preferably Surelease® E-7-7050 are used instead of ethylcellulose.   
     
     
         28 . The storage stable pharmaceutical preparation of  claim 1 ,
 characterized in that the preparation has been formulated for oral, nasal, rectal application or for application by inhalation.   
     
     
         29 . The storage stable pharmaceutical preparation of  claim 1 ,
 characterized in that the preparation is a tablet, pill, capsule, granule and/or powder.   
     
     
         30 . The storage stable pharmaceutical preparation of  claim 1 ,
 characterized in that the preparation or precursors thereof are produced by build-up and/or break-down granulation.   
     
     
         31 . The storage stable pharmaceutical preparation of  claim 1 ,
 characterized in that the preparation or precursors thereof are produced by extrusion.   
     
     
         32 . The storage stable pharmaceutical preparation of  claim 1 ,
 characterized in that the preparation can be stored over a period of at least 2 years under standard conditions (60% relative humidity, 25° C.) in accordance with admission guidelines.