Tamper-resistant dosage form containing ethylene-vinyl acetate polymer

• US 10,624,862 B2
• Filed: 07/10/2014
• Issued: 04/21/2020
• Est. Priority Date: 07/12/2013
• Status: Active Grant

• Current Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Original Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Inventors: Wening, Klaus, Barnscheid, Lutz, Schwier, Sebastian, Geissler, Anja
• Primary Examiner(s): Barham, Bethany P
• Assistant Examiner(s): Frazier, Barbara S
• Application Number:
  US14/327,671
• Publication Number:
  US 20150017250A1
• Time in Patent Office: 2,112 Days
• Field of Search: None
• CPC Class Codes: A61K 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: B29C 48/0011 combined with compression moulding
• CPC Class Codes: B29C 48/05 Filamentary, e.g. strands
• CPC Class Codes: B29C 51/002 characterised by the choice of material
• CPC Class Codes: B29K 2023/083 EVA, i.e. ethylene vinyl acetate copolymer
• CPC Class Codes: B29K 2105/0085 Copolymers

Abstract

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.

Claims

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.