Tamper-resistant dosage form containing ethylene-vinyl acetate polymer
The invention relates to a tamper-resistant, oral pharmaceutical dosage form comprising a pharmacologically active ingredient having psychotropic action and an ethylene-vinyl acetate (EVA) polymer which provides resistance against solvent extraction, resistance against grinding, and resistance against dose-dumping in aqueous ethanol.
1. A tamper-resistant, oral pharmaceutical dosage form comprising a homogeneous mixture of: (A) a pharmacologically active ingredient having psychotropic action and (B) a prolonged release matrix comprising 55 to 80 wt.-% relative to a total weight of the dosage form of an ethylene-vinyl acetate (EVA) polymer, wherein the EVA polymer provides resistance against solvent extraction, resistance against grinding, and resistance against dose-dumping in aqueous ethanol.
2. The pharmaceutical dosage form according to claim 1 , wherein the EVA polymer comprises repetition units derived from ethylene and vinyl acetate and/or vinyl alcohol.
3. The pharmaceutical dosage form according to claim 1 , wherein the EVA polymer contains at least 50 wt.-% of ethylene repetition units, relative to the total weight of the EVA polymer.
4. The pharmaceutical dosage form according to claim 3 , wherein the EVA polymer contains from 50 to 95 wt.-% of ethylene repetition units, relative to the total weight of the EVA polymer.
5. The pharmaceutical dosage form according to claim 1 , wherein the EVA polymer has a melt flow rate at 190° C. and 2.16 kg within the range of from 1 to 160 g/10 min measured according to ASTM D1238.
6. The pharmaceutical dosage form according to claim 1 , which is monolithic and has a breaking strength of at least 300 N.
7. The pharmaceutical dosage form according to claim 1 , which is monolithic and has an extension in any direction of at least 2.0 mm.
8. The pharmaceutical dosage form according to claim 1 , wherein the pharmacologically active ingredient is an opioid or a physiologically acceptable salt thereof.
9. The pharmaceutical dosage form according to claim 1 , which is hot-melt extruded.
10. A process for the production of the tamper-resistant, oral pharmaceutical dosage form according to claim 1 , said process comprising the steps of:
(i) mixing a pharmacologically active ingredient, 55 to 80 wt.-% relative to a total weight of the dosage form of an ethylene-vinyl acetate (EVA) polymer, and optionally further excipients to form a mixture; and
(ii) thermoforming the mixture obtained in step (i), wherein said mixture is simultaneously or before or after the application of heat subjected to pressure.
11. A tamper-resistant, oral pharmaceutical dosage form obtained by the process according to claim 10 .
12. A method of treating pain in a patient, said method comprising administering to said patient a dosage form according to claim 1 wherein the pharmacologically active ingredient is an opioid or a physiologically acceptable salt thereof.
13. The pharmaceutical dosage form according to claim 1 , which is multiparticulate, wherein at least a fraction of individual particles have a breaking strength of at least 300 N.
14. The pharmaceutical dosage form according to claim 1 , which is multiparticulate, wherein individual drug-containing particles have an extension in any direction of at least 2.0 mm.