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 LT100®), galactomannan (Meyprogat 150®), tara bean flour (Polygum 43/1C)), 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 180®). 
     
     
         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 . 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 . 
     
     
         33 . A method according to  claim 32 , wherein the therapeutic condition is pain. 
     
     
         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 30 . 
     
     
         35 . A method according to  claim 34 , wherein the therapeutic condition is pain. 
     
     
         36 . The dosage form according to  claim 1 , wherein the content of component (C) is at least 60 wt. %, relative to the total weight of the dosage form. 
     
     
         37 . The dosage form according to  claim 5 , wherein the content of component (C) is at least 60 wt. %, relative to the total weight of the dosage form. 
     
     
         38 . The dosage form according to  claim 10 , which comprises an opioid, wherein the opioid is selected from the group consisting of hydromorphone, morphine, oxycodone, oxymorphone, tramadol, (1R*,2R*)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)-phenol, and the physiologically acceptable salts thereof. 
     
     
         39 . The dosage form according to  claim 1 , wherein the one or more active ingredients with abuse potential (A) comprise oxycodone or a physiologically acceptable salt thereof; wherein the at least one synthetic or natural polymer (C) comprises a polyethylene oxide having a molecular weight of 1-15 million according to rheological measurements; and wherein the content of said polyethylene oxide is at least 60 wt. %, relative to the total weight of the dosage form. 
     
     
         40 . The dosage form according to  claim 1 , which additionally comprises at least one physiologically acceptable auxiliary substance (B). 
     
     
         41 . The dosage form according to  claim 1 , which additionally comprises at least one wax (D). 
     
     
         42 . The dosage form according to  claim 1 , which additionally comprises at least one physiologically acceptable auxiliary substance (B) and at least one wax (D). 
     
     
         43 . The dosage form according to  claim 1 , wherein the at least one synthetic or natural polymer (C) comprises a polyethylene oxide having a molecular weight of at least 0.5 million according to rheological measurements. 
     
     
         44 . The dosage form according to  claim 43 , wherein the polyethylene oxide has a molecular weight of 0.5-15 million according to rheological measurements. 
     
     
         45 . The dosage form according to  claim 44 , wherein the polyethylene oxide has a molecular weight of at least 600,000 according to rheological measurements. 
     
     
         46 . The dosage form according to  claim 45 , wherein the polyethylene oxide has a viscosity at 25° C. measured on a 5 wt. % aqueous solution using a model RVF Brookfield viscosimeter (spindle no. 2/rotational speed 2 rpm) of 4500 to 17600 cP. 
     
     
         47 . The dosage form according to  claim 44 , wherein the polyethylene oxide has a molecular weight of at least 1,000,000 according to rheological measurements. 
     
     
         48 . The dosage form according to  claim 47 , wherein the polyethylene oxide has a viscosity at 25° C. measured on a 2 wt. % aqueous solution using a model RVF Brookfield viscosimeter (spindle no. 1 or 3/rotational speed 10 rpm) of 400 to 4000 cP. 
     
     
         49 . The dosage form according to  claim 44 , wherein the polyethylene oxide has a molecular weight of at least 4,000,000 according to rheological measurements. 
     
     
         50 . The dosage form according to  claim 49 , wherein the polyethylene oxide has a viscosity at 25° C. measured on a 1 wt. % aqueous solution using a model RVF Brookfield viscosimeter (spindle no. 2/rotational speed 2 rpm) of 1650 to 10000 cP. 
     
     
         51 . A method of reducing the incidence of drug abuse of an active ingredient (A) with abuse potential, said method comprising providing said active ingredient (A) in the form of a dosage form according to  claim 1 .