FORM OF ADMINISTRATION SECURED AGAINST MISUSE
The invention relates to a form of administration 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.
1 . An abuse-proofed dosage form thermoformed without extrusion, comprising one or more active ingredients with abuse potential (A), optionally one or more physiologically acceptable auxiliary substances (B), at least one synthetic or natural polymer (C) and optionally at least one wax (D), wherein the one or more active ingredients with abuse potential (A) are selected from the group consisting of oxymorphone, hydromorphone, morphine and physiologically acceptable compounds and derivatives thereof, and wherein the dosage form 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 , which comprises 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 the polymer (C) is a polyethylene oxide (C) having 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 as the wax (D) 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 . (canceled)
11 . (canceled)
12 . 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, and
(f) at least one bitter substance.
13 . A dosage form according to claim 12 , 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.
14 . 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.
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 a 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 a constituent of the hot substance drug is at least one constituent selected from the group consisting of myristicin, elemicin, isoeugenol, O-asarone, safrole, gingerols, xanthorrhizol, capsaicinoids and a compound derived from these constituents.
18 . A dosage form according to claim 12 , wherein component (b) is at least one viscosity-increasing agent selected from the group consisting of microcrystalline cellulose with 11 wt. % carboxymethylcellulose sodium, carboxymethylcellulose sodium, polyacrylic acid, locust bean flour, pectins from citrus fruit or apples, waxy maize starch, sodium alginate, guar flour, iota carrageen, karaya gum, gellan gum, galactomannan, tara bean flour, propylene glycol alginate, apple pectin, sodium hyaluronate, tragacanth, tara gum, fermented polysaccharide welan gum, and xanthan gum.
19 . A dosage form according to claim 12 , wherein component (c) 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 derivative thereof.
20 . A dosage form according to claim 12 , wherein component (c) is at least one neuroleptic as a stimulant antagonist.
21 . A dosage form according to claim 12 , wherein the component (d) emetic is based on one or more constituents of ipecacuanha (ipecac) root and/or is apomorphine.
22 . A dosage form according to claim 12 , wherein component (e) is at least one physiologically acceptable dye.
23 . A dosage form according to claim 12 , wherein component (f) is at least one bitter substance selected from the group consisting of aromatic oils, fruit aroma substances, and denatonium benzoate and mixtures thereof comprising at least 2 components.
24 . A dosage form according to claim 12 , which comprises at least one of components (c), (d) and/or (f), wherein the active ingredient or active ingredients (A) is/are spatially separated from component (c) and/or (d) and/or (f).
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, mixing components (A), (B), (C) and the optionally present component (D) to form a mixture, granulating the mixture and, optionally after granulation, shaping by application of force with preceding or simultaneous exposure to heat to yield the dosage form.
29 . A process according to claim 28 , wherein granulation is performed by melt granulation or wet granulation.
30 . A dosage form obtained by a process according to claim 28 .
31 . A dosage form according to claim 1 , wherein the physiologically acceptable compounds and derivatives are salts, solvates, esters, ethers and amides.
32 . A method of treating pain comprising administering to a patient in need thereof a effective amount to treat pain of one or more active ingredients with abuse potential (A) selected from the group consisting of oxymorphone, hydromorphone, morphine and physiologically acceptable compounds and derivatives thereof, wherein said one or more active ingredients with abuse potential (A) are administered to said patient in the form of a dosage form according to claim 1 .