Abuse-proofed oral dosage form
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, characterised in that it comprises at least one opioid with potential for abuse (A) and/or one of the physiologically acceptable compounds thereof, at least one synthetic or natural polymer (C), optionally delayed-release auxiliary substances, optionally 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.
2 . A dosage form according to claim 1 , characterised in that the opioid is at least one opioid selected from among the group comprising oxycodone, hydromorphone, morphine, tramadol, the stereoisomers thereof, the enantiomers thereof, the diastereomers thereof in any desired mixtures, the physiologically acceptable compounds thereof, preferably salts and solvates and the derivatives thereof, preferably esters or ethers.
3 . A dosage form according to claim 1 , characterised in that, the opioid used was at least one opioid selected from among the group comprising (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, the physiologically acceptable salts thereof, preferably hydrochlorides, physiologically acceptable enantiomers, stereoisomers, diastereoisomers and racemates and the physiologically acceptable derivatives thereof, preferably ethers, esters or amides.
4 . A dosage form according to claim 1 , characterised in that it is in the form of a tablet.
5 . A dosage form according to claim 1 , characterised in that it is in multiparticulate form, preferably in the form of microtablets, micropellets, granules, spheroids, beads or pellets, optionally press-moulded into tablets or packaged in capsules.
6 . A dosage form according to claim 1 , characterised in that the polymer (C) is at least one polymer selected from among the group comprising polyethylene oxides, polyethylenes, polypropylenes, polyvinyl chlorides, polycarbonates, polystyrenes, polyacrylates, and the copolymers thereof, preferably a polyethylene oxide.
7 . A dosage form according to claim 6 , characterised in that the polyethylene oxide is of high molecular weight.
8 . A dosage form according to claim 6 , characterised in that the polymer (C) is a water-soluble or water-swellable polymer.
9 . A dosage form according to claim 1 , characterised in that the wax (D) is at least one natural, semi-synthetic or synthetic was with a softening point of =60° C.
10 . A dosage form according to claim 9 , characterised in that the wax (D) is carnauba wax or beeswax.
11 . A dosage form according to claim 1 , characterised in that the component(s) (C) and optionally (D) are present in such quantities that the dosage form exhibits a breaking strength of at least 500 N, preferably of 1000 N.
12 . A dosage form according to claim 1 , characterised in that the active ingredient is present in a delayed-release matrix.
13 . A dosage form according to claim 1 , characterised in that component (C) and/or component (D) also serves as an additional delayed-release component.
14 . A dosage form according to claim 1 , characterised in that it comprises a delayed-release coating.
15 . A dosage form according to claim 1 , characterised in that it comprises at least one of the following components (a)-(f) as the 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, preferably as an aqueous extract obtained from the dosage form, forms a gel which preferably remains visually distinguishable when introduced into a further quantity of an aqueous liquid,
(c) at least one antagonist for each of the opioids with potential for abuse,
(d) at least one emetic,
(e) at least one dye as an aversive agent,
(f) at least one bitter substance.
16 . A dosage form according to claim 1 , characterised in that it comprises as the viscosity-increasing agent at least one polymer selected from among the group comprising 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.
17 . A dosage form according to claim 1 , characterised in that component (C) serves as an additional viscosity-increasing agent.
18 . A process for the production of a dosage form according to claim 1 , characterised in that
(1) components (A), (C), optionally (B) and optionally (D) and optionally delayed-release matrix compounds are mixed and
(2) the resultant mixture, optionally after pelletisation, is formed into the dosage form by application of force optionally with preceding or simultaneous exposure to heat and is optionally provided with a delayed-release coating.
19 . A process according to claim 18 , characterised in that pelletisation is performed by a melt method.
20 . A process according to claim 18 , characterised in that pelletisation is performed by wet method.
21 . A process for the production of a dosage form according to claim 1 , characterised in that
(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 force until the formed articles exhibit breaking hardness of at least 500 N, preferably of 1000 N,
(4) are optionally provided with an optionally delayed-release coating and the formed articles are optionally all mixed together again.
22 . A dosage form obtainable by processes according to claim 18.