Abuse-proofed dosage form

Abstract

The present invention relates to an abuse-proofed, thermoformed dosage form containing, in addition to one or more active ingredients with abuse potential optionally together with physiologically acceptable auxiliary substances, at least one synthetic or natural polymer with a breaking strength of at least 500 N and to a process for the production thereof.

1 . An abuse-proofed, thermoformed dosage form comprising one or more active ingredients with abuse potential (A) optionally together with physiologically acceptable auxiliary substances (B), at least one synthetic or natural polymer (C) and optionally at least one wax (D), wherein component (C) exhibits a breaking strength of at least 500 N. 
     
     
         2 . A dosage form according to  claim 1 , which is in the form of a tablet. 
     
     
         3 . A dosage form according to  claim 1 , which is in multiparticulate form. 
     
     
         4 . A dosage form according to  claim 1 , wherein the polymer (C) is at least one polymer selected from the group consisting of polyethylene oxide, polymethylene oxide, polypropylene oxide, polyethylene, polypropylene, polyvinyl chloride, polycarbonate, polystyrene, polyacrylate, copolymers and mixtures thereof. 
     
     
         5 . A dosage form according to  claim 1 , wherein the polymer (C) has a molecular weight of at least 0.5 million according to rheological measurements. 
     
     
         6 . A dosage form according to  claim 5 , wherein the molecular weight is 1-15 million. 
     
     
         7 . A dosage form according to  claim 1 , which comprises the wax (D) and the wax (D) is at least one natural, semi-synthetic or synthetic wax with a softening point of at least 60° C. 
     
     
         8 . A dosage form according to  claim 7 , wherein the wax (D) is carnauba wax or beeswax. 
     
     
         9 . A dosage form according to  claim 1 , wherein the component(s) (C) is/are present in quantities such that the dosage form has a breaking strength of at least 500 N. 
     
     
         10 . A dosage form according to  claim 1 , wherein the active ingredient (A) is at least one active ingredient selected from the group consisting of opiates, opioids, tranquillisers, stimulants, barbiturates and further narcotics. 
     
     
         11 . A dosage form according to  claim 1 , which additionally comprises at least one of the following components a)-f):
 (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 with the extract obtained from the dosage form, which gel optionally remains visually distinguishable when introduced into a further quantity of an aqueous liquid,   c) at least one antagonist for the active ingredient or active ingredients with abuse potential,   (d) at least one emetic,   (e) at least one dye as an aversive agent,   (f) at least one bitter substance.   
     
     
         12 . A dosage form according to  claim 11 , wherein the component (a) irritant substance causes burning, itching, an urge to sneeze, increased formation of secretions or a combination of at least two of these stimuli. 
     
     
         13 . A dosage form according to  claim 12 , wherein the component (a) irritant substance is based on one or more constituents of at least one hot substance drug. 
     
     
         14 . A dosage form according to  claim 13 , wherein the hot substance drug is at least one drug selected from the group consisting of  Allii sativi  bulbus (garlic),  Asari  rhizoma cum herba ( Asarum  root and leaves),  Calami  rhizoma (calamus root),  Capsici  fructus ( capsicum ),  Capsici  fructus acer (cayenne pepper),  Curcumae longae  rhizoma (turmeric root),  Curcumae xanthorrhizae  rhizoma (Javanese turmeric root),  Galangae  rhizoma (galangal root),  Myristicae  semen (nutmeg),  Piperis nigri  fructus (pepper),  Sinapis albae  semen (erucae/white mustard seed),  Sinapis nigri  semen (black mustard seed),  Zedoariae  rhizoma (zedoary root) and  Zingiberis  rhizoma (ginger root). 
     
     
         15 . A dosage form according to  claim 13 , wherein the constituent of the hot substance drug is an o-methoxy(methyl)phenol compound, an acid amide compound, a mustard oil or a sulfide compound or is derived from such a compound. 
     
     
         16 . A dosage form according to  claim 13 , wherein the constituent of the hot substance drug is at least one constituent selected from the group consisting of myristicin, elemicin, isoeugenol, β-asarone, safrole, gingerols, xanthorrhizol, capsaicinoids, piperine, glucosinolates, and a compound derived from these constituents. 
     
     
         17 . A dosage form according to  claim 11 , wherein component (b) is at least one viscosity-increasing agent selected from the group consisting of microcrystalline cellulose with 11 wt. % carboxymethylcellulose sodium (Avicel® RC 591), carboxymethylcellulose sodium (Blanose®, CMC-Na C300P®, Frimulsion BLC-5®, Tylose C300 P®), polyacrylic acid (Carbopol® 980 NF, Carbopol® 981), locust bean flour (Cesagum® LA-200, Cesagum® LID/150, Cesagum® LN-1), citrus pectin (Cesapectin® HM Medium Rapid Set), waxy maize starch (C*Gel 04201®), sodium alginate (Frimulsion ALG (E401)®), guar flour (Frimulsion BM®, Polygum 26/1-75®), iota carrageen (Frimulsion D021®), karaya gum, gellan gum (Kelcogel F®, Kelcogel LT1000), galactomannan (Meyprogat 150®), tara bean flour (Polygum 43/1®), propylene glycol alginate (Protanal-Ester SD-LB®), sodium hyaluronate, apple pectin, pectin from lemon peel, sodium hyaluronate, tragacanth, tara gum (Vidogum SP 200®), fermented polysaccharide welan gum (K1A96) and xanthan gum (Xantural 1800). 
     
     
         18 . A dosage form according to  claim 11 , wherein component (c) is at least one opiate or opioid antagonist selected from the group consisting of naloxone, naltrexone, nalmefene, nalid, nalmexone, nalorphine, naluphine and a corresponding physiologically acceptable compound. 
     
     
         19 . A dosage form according to  claim 11 , wherein the component (c) is at least one neuroleptic stimulant antagonist. 
     
     
         20 . A dosage form according to  claim 11 , wherein the component (d) emetic is based on one or more constituents of  radix ipecacuanha  (ipecac root) and/or is apomorphine. 
     
     
         21 . A dosage form according to  claim 11 , wherein component (e) is at least one physiologically acceptable dye. 
     
     
         22 . A dosage form according to  claim 11 , wherein component (f) is at least one bitter substance selected from the group consisting of aromatic oils, fruit aroma substances, denatonium benzoate and mixtures thereof. 
     
     
         23 . A dosage form according to  claim 11 , wherein the active ingredient or active ingredients (A) is/are spatially separated from component (c) and/or (d) and/or (f), wherein the active ingredient or active ingredients (A) is/are optionally present in at least one subunit (X) and components (c) and/or (d) and/or (f) is/are present in at least one subunit (Y), and, when the dosage form is correctly administered, components (c) and/or (d) and/or (f) from subunit (Y) do not exert their effect in the body and/or on taking. 
     
     
         24 . A dosage form according to  claim 1 , which comprises at least one active ingredient at least partially in controlled release form. 
     
     
         25 . A dosage form according to  claim 24 , wherein each of the active ingredients with abuse potential (A) is present in a controlled release matrix. 
     
     
         26 . A dosage form according to  claim 25 , wherein component (C) and/or component (D) also serve as a controlled release matrix material. 
     
     
         27 . A process for the production of a dosage form according to  claim 1 , comprising:
 mixing components (A), (B), (C) and the optionally present component (D) and the optionally present components (a) to (f) to form a resultant mixture, and   press-forming the resultant mixture, optionally after granulation, to yield the dosage form with preceding, simultaneous, or subsequent exposure to heat.   
     
     
         28 . A process according to  claim 27 , wherein granulation is performed by means of a melt process. 
     
     
         29 . A process according to  claim 27 , which comprises press-forming the resultant mixture to yield a press-formed product, and exposing the press-formed product to heat to yield the dosage form. 
     
     
         30 . A dosage form obtainable by a process according to  claim 27 . 
     
     
         31 . A dosage form obtainable by a process according to  claim 29 . 
     
     
         32 . An abuse-proofed, thermoformed dosage form in the form of a tablet obtained by a process comprising:
 a) mixing:
 i) an opioid or a physiologically acceptable salt thereof; 
 ii) optionally physiologically acceptable substances (B); 
 iii) at least one polyalkylene oxide (C) having a molecular weight of 1-15 million according to rheological measurements; and 
 iv) optionally at least one wax (D); 
   to form a resultant mixture;   b) pressing forming the resultant mixture to form a press-formed product; and   c) exposing the press-formed product to heat to yield the dosage form.   
     
     
         33 . A dosage form according to  claim 32 , wherein the opioid or physiologically acceptable salt thereof is oxycodone or a physiologically acceptable salt thereof. 
     
     
         34 . A method of treating a therapeutic condition in a patient suffering therefrom, said method comprising administering to said patient a dosage form according to  claim 1 . 
     
     
         35 . A method according to  claim 34 , wherein the therapeutic condition is pain. 
     
     
         36 . A method of treating a therapeutic condition in a patient suffering therefrom, said method comprising administering to said patient a dosage form according to  claim 32 . 
     
     
         37 . A method according to  claim 36 , wherein the therapeutic condition is pain.