Abuse-proofed oral dosage form

Abstract

The present invention relates to an abuse-proofed, oral dosage form with controlled opioid-release for once daily administration, characterised in that it comprises at least one opioid with potential for abuse (A), at least one synthetic or natural polymer (C), optionally delayed-release matrix auxiliary substances, physiologically acceptable auxiliary substances (B), optionally a wax (D) and optionally at least one delayed-release coating, component (C) or (D) in each case exhibiting a breaking strength of at least 500 N, preferably of at least 1000 N.

1 . An abuse-proofed oral dosage form with controlled opioid release for once daily administration, comprising at least one opioid with potential for abuse (A) and/or one of the physiologically acceptable compounds thereof, polyethylene oxide having a molecular weight of 0.5 million to 15 million (C), optionally delayed release auxiliary substances, optionally physiologically acceptable auxiliary substances (B), optionally a wax (D) and optionally at least one delayed-release coating, said abuse-proofed oral dosage form exhibiting a breaking strength of at least 500 N. 
     
     
         2 . A dosage form according to  claim 1 , wherein the opioid is at least one opioid selected from the group consisting of oxycodone, hydromorphone, morphine, tramadol, the stereoisomers thereof, the enantiomers thereof, the diastereomers thereof in any desired mixtures and the physiologically acceptable compounds thereof. 
     
     
         3 . The dosage form of  claim 2 , wherein said physiologically acceptable compounds thereof are salts, solvates, esters or ethers. 
     
     
         4 . A dosage form according to  claim 1 , wherein said at least one opioid is selected from the group consisting of (2R,3R)-1-dimethylamino-3-(3-methoxyphenyl)-2-methyl-pentan-3-ol, (1RS,3RS,6RS)-6-dimethylaminomethyl-1-(3-methoxyphenyl)-cyclohexane-1,3-diol, (1RS,2RS)-3-(2-dimethylaminomenthyl-cyclohexyl)phenol, physiologically acceptable salts thereof, physiologically acceptable enantiomers thereof, stereoisomers thereof, diastereoisomers thereof, and racemates thereof and ethers, esters or amides thereof. 
     
     
         5 . A dosage form according to  claim 1 , wherein said at least one opioid is selected from the group consisting of hydrocodone, the stereoisomers thereof, the enantiomers thereof, the diastereomers thereof in any desired mixtures and the physiologically acceptable compounds thereof. 
     
     
         6 . The dosage form of  claim 5 , wherein said physiologically acceptable compounds thereof are salts, solvates, esters or ethers. 
     
     
         7 . A dosage form according to  claim 1 , in the form of a tablet. 
     
     
         8 . A dosage form according to  claim 1 , wherein said wax (D) is present and is at least one natural, semi-synthetic or synthetic wax with a softening point of at least 60° C. 
     
     
         9 . A dosage form according to  claim 8 , wherein said wax (D) is carnauba wax or beeswax. 
     
     
         10 . A dosage form according to  claim 1 , wherein said active ingredient is present in a delayed-release matrix. 
     
     
         11 . A dosage form according to  claim 1 , wherein component (C) and/or component (D) also serves as an additional delayed-release auxiliary substance. 
     
     
         12 . A dosage form according to  claim 1 , comprising said delayed-release coating. 
     
     
         13 . A dosage form according to  claim 1 , comprising at least one of the following components (a)-(f) as an auxiliary substance (B): (a) at least one substance which irritates the nasal passages and/or pharynx, (b) at least one viscosity-increasing agent, which, with the assistance of a necessary minimum quantity of an aqueous liquid, forms a gel which optionally remains visually distinguishable when introduced into a further quantity of an aqueous liquid, (c) at least one antagonist for said at least one opioid, (d) at least one emetic, (e) at least one dye as an aversive agent, (f) at least one bitter substance. 
     
     
         14 . A dosage form according to  claim 13 , wherein said viscosity-increasing agent is present and comprises at least one polymer selected from the group consisting of carboxymethylcellulose sodium, polyacrylic acid, locust bean flour, pectin, waxy maize starch, alginate, guar flour, iota-carrageenan, karaya gum, gellan gum, galactomannan, tara stone flour, propylene glycol alginate, hyaluronate, tragacanth, tara gum, fermented polysaccharide welan gum and xanthan. 
     
     
         15 . A dosage form according to  claim 1 , wherein component (C), in addition to increasing the breaking strength of the dosage form, also functions as a viscosity-increasing agent. 
     
     
         16 . A dosage form according to  claim 1 , wherein component(s) (C) and optionally (D) are present in sufficient amounts to produce a dosage form exhibiting a breaking strength of at least 500 N. 
     
     
         17 . A dosage form according to  claim 1 , exhibiting a breaking strength of at least 1000N. 
     
     
         18 . A process for the production of the dosage form of  claim 1 , which comprises (1) mixing components (A), (C), optionally an auxiliary substance (B) selected from the group consisting of (a) at least one substance which irritates the nasal passages and/or pharynx, (b) at least one viscosity-increasing agent, which, with the assistance of a necessary minimum quantity of an aqueous liquid, forms a gel which optionally remains visually distinguishable when introduced into a further quantity of an aqueous liquid, (c) at least one antagonist for said at least one opioid, (d) at least one emetic, (e) at least one dye as an aversive agent, (f) at least one bitter substance, optionally (D) and optionally delayed-release matrix compounds to form a mixture and (2) forming the resultant mixture, optionally after pelletisation, into the dosage form by application of force, with preceding or simultaneous heating to at least the softening point of component (C), of sufficient magnitude and for a sufficient time until the dosage form exhibits a breaking strength of at least 500N, and optionally applying a delayed-release coating. 
     
     
         19 . The process of  claim 18 , wherein said pelletisation is performed and is performed by a melt method. 
     
     
         20 . The process of  claim 18 , where said pelletisation is performed and is performed by wet method. 
     
     
         21 . The process of  claim 18 , wherein (1) a mixture containing components (A), (C), optionally (B) and optionally (D) and optionally delayed-release matrix compounds is formed into formed articles by application of force, (2) the formed articles obtained are optionally singulated and optionally in each case graded by size and (3) after or during heating to at least the softening point of component (C), the formed articles are exposed to a force of sufficient magnitude and for a sufficient time until the formed articles exhibit a breaking strength of at least 500 N, (4) the formed articles are optionally provided with an optionally delayed-release coating and the formed articles are optionally all mixed together again. 
     
     
         22 . The process of  claim 21 , wherein said breaking strength is at least 1000N. 
     
     
         23 . A dosage form obtained by the process of  claim 18 . 
     
     
         24 . A method of treating pain in a patient in need of such treating, said method comprising administering to said patient a dosage form according to  claim 1 . 
     
     
         25 . A method of treating pain in a patient in need of such treating, said method comprising administering to said patient a dosage form according to  claim 23 .