Abuse-proofed dosage forms

Abstract

The invention relates to a form of administration which is secured against misuse and which is thermoformed without extrusion, comprising at least one synthetic or natural polymer having a resistance to breaking of at least 500 N in addition to one or several active ingredients with a misuse potential and, optionally physiologically compatible auxiliary substances. The invention also relates to a method for the production thereof.

We claim: 
     
         1 . An abuse-proofed dosage form thermoformed without extrusion, comprising one or more active ingredients with abuse potential (A), optionally physiologically acceptable auxiliary substances (B), at least one synthetic or natural polymer (C) and optionally at least one wax (D), wherein component (C) and the optionally present component (D) exhibit 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, optionally in the form of microtablets, micropellets, granules, spheroids, beads or pellets, optionally pressed into tablets or packaged in capsules. 
     
     
         4 . A dosage form according to  claim 1 , which contains as polymer (C) 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 the mixtures thereof. 
     
     
         5 . A dosage form according to  claim 1 , wherein polymer (C) is polyethylene, and the polyethylene oxide (C) has a molecular weight of at least 0.5 million. 
     
     
         6 . A dosage according to  claim 5 , wherein the molecular weight of the polyethylene oxide (C) is at least 1 million. 
     
     
         7 . A dosage form according to  claim 6 , wherein the molecular weight of the polyethylene oxide (C) is 1-15 million. 
     
     
         8 . A dosage form according to  claim 1 , which comprises a 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. 
     
     
         9 . A dosage form according to  claim 8 , wherein the wax (D) is carnauba wax or beeswax. 
     
     
         10 . A dosage form according to  claim 1 , wherein the component(s) (C) and optionally (D) is/are present in quantities such that the dosage form has a breaking strength of at least 500 N. 
     
     
         11 . A dosage form according to  claim 1 , wherein the active ingredient (A) is at least one active ingredient selected from the group consisting of opioids, tranquillisers, stimulants, barbiturates and further narcotics. 
     
     
         12 . A dosage form according to  claim 11 , 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.   
     
     
         13 . A dosage form according to  claim 12 , comprises a component (a) irritant substance that causes burning, itching, an urge to sneeze, increased formation of secretions or a combination of at least two of these stimuli. 
     
     
         14 . A dosage form according to  claim 13 , wherein the component (a) irritant substance is based on one or more constituents of at least one hot substance drug. 
     
     
         15 . A dosage form according to  claim 14 , 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 (white mustard seed),  Sinapis  nigri semen (black mustard seed), Zedoariae rhizoma (zedoary root) and Zingiberis rhizoma (ginger root). 
     
     
         16 . A dosage form according to  claim 14 , 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. 
     
     
         17 . A dosage form according to  claim 14 , 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. 
     
     
         18 . A dosage form according to  claim 12 , which comprises a component (b) that 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), pectins from citrus fruit or apples (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 LT100®), galactomannan (Meyprogat 150®), tara bean flour (Polygum 43/1®), propylene glycol alginate (Protanal-Ester SD-LB®), apple pectin, sodium hyaluronate, tragacanth, tara gum (Vidogum SP 200®), fermented polysaccharide welan gum (K1A96), and xanthan gum (Xantural 180®). 
     
     
         19 . A dosage form according to  claim 12 , which comprises a component (c) that is at least one opioid antagonist selected from the group consisting of naloxone, naltrexone, nalmefene, nalid, nalmexone, nalorphine, naluphine and a corresponding physiologically acceptable compound. 
     
     
         20 . A dosage form according to  claim 12 , which comprises a component (c) that is at least one neuroleptic as a stimulant antagonist. 
     
     
         21 . A dosage form according to  claim 12 , which comprises a component (d) emetic that is based on one or more constituents of ipecacuanha (ipecac) root and/or is apomorphine. 
     
     
         22 . A dosage form according to  claim 12 , which comprises a component (e) that is at least one physiologically acceptable dye. 
     
     
         23 . A dosage form according to  claim 12 , which comprises a component (f) that is at least one bitter substance selected from the group consisting of aromatic oils, fruit aroma substances, denatonium benzoate and mixtures thereof comprising at least 2 components. 
     
     
         24 . A dosage form according to  claim 12 , 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. 
     
     
         25 . A dosage form according to  claim 1 , which comprises at least one active ingredient at least partially in controlled release form. 
     
     
         26 . A dosage form according to  claim 25 , wherein each of the active ingredients with abuse potential (A) is present in a controlled release matrix. 
     
     
         27 . A dosage form according to  claim 26 , wherein component (C) and/or the optionally present component (D) also serve as a controlled release matrix material. 
     
     
         28 . A process for the production of a dosage form according to  claim 1 , comprising, without using an extruder,
 components (A), (B), (C) and the optionally present component (D) are mixed and the optionally present components (a) to (f) are co-mixed or, if necessary, are separated mixed with addition of component (C) and optionally (D)   and the resultant mixture or mixtures, optionally after granulation, is/are shaped by application of force to yield the dosage form with preceding or simultaneous exposure to heat.   
     
     
         29 . A process according to  claim 28 , wherein granulation is performed by melt granulation or wet granulation. 
     
     
         30 . A dosage form obtainable by a process according to  claim 28 .