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, comprising at least one opioid with potential for abuse (A) and/or one of the physiologically acceptable compounds or derivatives 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, wherein the at least one opioid with potential for abuse (A) is 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 , wherein the opioid is at least one opioid selected from among the group consisting of hydromorphone, morphine, the stereoisomers thereof, the enantiomers thereof, the diastereomers thereof in any desired mixtures, the physiologically acceptable compounds thereof, and the derivatives thereof.
3 . (canceled)
4 . A dosage form according to claim 1 , which is in the form of a tablet.
5 . A dosage form according to claim 1 , which is in multiparticulate form.
6 . A dosage form according to claim 1 , wherein the polymer (C) is at least one polymer selected from among the group consisting of polyethylene oxides, polyethylenes, polypropylenes, polyvinyl chlorides, polycarbonates, polystyrenes, polyacrylates, and the copolymers thereof.
7 . A dosage form according to claim 6 , wherein the polyethylene oxide is of high molecular weight.
8 . A dosage form according to claim 6 , wherein the polymer (C) is a water-soluble or water-swellable polymer.
9 . A dosage form according to claim 1 , wherein the wax (D) is at least one natural, semi-synthetic or synthetic wax with a softening point of at least 60° C.
10 . A dosage form according to claim 9 , wherein the wax (D) is carnauba wax or beeswax.
11 . A dosage form according to claim 1 , wherein the component(s) (C) and optionally (D) are present in such quantities that the dosage form exhibits a breaking strength of at least 1000 N.
12 . A dosage form according to claim 1 , wherein the at least one opioid with a potential for abuse (A) is present in a delayed-release matrix.
13 . A dosage form according to claim 12 , wherein component (C) and/or component (D) also serves as an additional delayed-release component.
14 . A dosage form according to claim 1 , which comprises a delayed-release coating.
15 . A dosage form according to claim 1 , which 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, forms a gel which optionally 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, and
(f) at least one bitter substance.
16 . A dosage form according to claim 15 , which comprises at least one polymeric viscosity-increasing agent selected from among the group consisting of 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 16 , wherein component (C) serves as an additional viscosity-increasing agent.
18 . A process for the production of a dosage form according to claim 1 , which comprises:
(1) mixing components (A), (C), optionally (B) and optionally (D) and optionally delayed-release matrix compounds to form a mixture, and
(2) forming the mixture, optionally after pelletisation, into the dosage form by application of force optionally with preceding or simultaneous exposure to heat and optionally providing the dosage form with a delayed-release coating.
19 . A process according to claim 18 , wherein pelletisation is performed by a melt method.
20 . A process according to claim 18 , wherein pelletisation is performed by wet pelletisation.
21 . A process for the production of a dosage form according to claim 1 , which comprises:
(1) forming a mixture containing components (A), (C), optionally (B) and optionally (D) and optionally delayed-release matrix compounds into formed articles by application of force,
(2) optionally singulating the formed articles and optionally in each case grading by size, and
(3) exposing the formed articles to force, after or during heating to at least the softening point of component (C), until the formed articles exhibit a breaking hardness of at least 500 N, and
(4) optionally providing the formed articles with an optionally delayed-release coating and optionally mixing the formed articles together again.
22 . A dosage form obtained by a process according to claim 18 .
23 . A dosage form according to claim 1 , wherein the physiologically acceptable compounds and derivatives are salts, solvates, esters, ethers and amides.
24 . A dosage form obtained by a process according to claim 21 .
25 . A method of treating pain comprising administering to a patient in need thereof a effective amount to treat pain of at least one opioid with potential for abuse (A) selected from the group consisting of oxymorphone, hydromorphone, morphine and physiologically acceptable compounds and derivatives thereof, wherein said at least one opioid with potential for abuse (A) is administered to said patient in the form of a dosage form according to claim 1 .