Process for the production of an abuse-proofed solid dosage form
The present invention relates to a process for the production of an abuse-proofed solid dosage form containing at least one active ingredient with potential for abuse and a binder with a breaking strength of =500 N, by exposing a mixture comprising the active ingredient and the binder to ultrasound and force.
1 . A process for the production of an abuse-proofed solid dosage form containing at least one active ingredient with potential for abuse and at least one binder with a breaking strength of =500 N, characterised in that a mixture comprising the active ingredient and the binder is exposed to ultrasound and force.
2 . A process according to claim 1 , characterised in that the dosage form is an oral dosage form.
3 . A process according to claim 1 , characterised in that the active ingredient used is at least one active ingredient selected from among the group comprising opioids, opiates, stimulants and further narcotics and the physiologically acceptable derivatives thereof.
4 . A process according to claim 3 , characterised in that the physiologically acceptable derivatives are salts, solvates, esters, ethers or amides.
5 . A process according to claim 1 , characterised in that the active ingredient with potential for abuse which is used is oxycodone, morphine, hydromorphone, tramadol or the physiologically acceptable salts thereof.
6 . A process according to claim 1 , characterised in that the binder is present in a quantity of at least 20 wt. %, preferably of at least 35 wt. %, particularly preferably of 50 to 99.9% wt. %, relative to the total weight of the dosage form.
7 . A process according to claim 1 , characterised in that the binder which is used is at least one synthetic or natural polymer and optionally a wax, in each case with a breaking strength of at least 500 N.
8 . A process according to claim 7 , characterised in that the polymer exhibits a viscosity at 25° C. of 4500 to 17600 cP, measured on a 5 wt. % aqueous solution with the assistance of a Brookfield viscosimeter.
9 . A process according to claim 7 , characterised in that the polymer 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 polyethylene oxide.
10 . A process according to claim 9 , characterised in that the polyethylene oxide has a molecular weight of at least 1 million, particularly preferably of at least 5 million.
11 . A process according to claim 1 , characterised in that, apart from the active ingredient with potential for abuse and the binder, the dosage form also contains further conventional auxiliary substances.
12 . A process according to claim 11 , characterised in that the dosage form contains a plasticiser, preferably a low molecular weight polyethylene glycol, as the auxiliary substance.
13 . A process according to claim 1 , characterised in that the applied ultrasound has a frequency of 1 kHz to 2 MHz, preferably of 20 to 40 kHz.
14 . A process according to any one of claim 1 , characterised in that there is direct contact between the mixture and the ultrasound source during ultrasonication.
15 . A process according to claim 1 , characterised in that ultrasonication proceeds until the binder has softened.
16 . A process according to claim 1 , characterised in that shaping of the mixture proceeds by compaction during or after ultrasonication or by extrusion with rollers and/or by calendering during or after ultrasonication.
17 . A process according to claim 16 , characterised in that a force is applied for the purpose of compaction.
18 . A process according to claim 16 , characterised in that, for compaction, the mixture is already in the form of powder, pellets, microparticles or granules, which have been produced by conventional processes.
19 . A process according to claim 1 , characterised in that the mixture is shaped into tablets.
20 . A process according to claim 1 , characterised in that the mixture is shaped into a multiparticulate final shape, preferably pellets, microcapsules, microparticles, granules.