TAMPER-RESISTANT DOSAGE FORM FOR OXIDATION-SENSITIVE OPIOIDS

• US 20110020451A1
• Filed: 07/21/2010
• Published: 01/27/2011
• Est. Priority Date: 07/22/2009
• Status: Abandoned Application

• Current Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Original Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Inventors: Grießmann, Kornelia, Bertram, Ulrike, BARTHOLOMÄUS, Johannes, Geißler, Anja
• Application Number:
  US12/840,471
• Publication Number:
  US 20110020451A1
• Time in Patent Office: Days
• US Class Current: 424/486
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 9/20 Pills, tablets, discs, rods A61K9/0004, A61K9/0007, A61K9/0056, A61K9/0065 take precedence; for reconstitution of a drink A61K9/0095
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• 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: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61K 9/284 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/30 for treating abuse or dependence

Abstract

Thermoformed pharmaceutical dosage form having a breaking strength of at least 300 N, comprising

• • an opioid (A),
  • a free physiologically acceptable acid (B) in an amount of from 0.001 to 5.0 wt.-%, based on the total weight of the pharmaceutical dosage form, and
  • a polyalkylene oxide (C) having a weight average molecular weight M_w of at least 200,000 g/mol.

Claims

1. A thermoformed pharmaceutical dosage form having a breaking strength of at least 300 N and comprising

an opioid (A),

a free physiologically acceptable acid (B) in an amount of from 0.001 to 5.0 wt.-%, based on the total weight of the pharmaceutical dosage form, and

a polyalkylene oxide (C) having a weight average molecular weight M_w of at least 200,000 g/mol.

2. The pharmaceutical dosage form according to claim 1, wherein the acid (B) is a multicarboxylic acid.

3. The pharmaceutical dosage form according to claim 2, wherein the multicarboxylic acid is selected from the group consisting of maleic acid, fumaric acid, glutaric acid, malonic acid and citric acid.

4. The pharmaceutical dosage form according to claim 1, wherein the content of the acid (B) is within the range of from 0.005 to 2.5 wt.-%, based on the total weight of the pharmaceutical dosage form.

5. The pharmaceutical dosage form according to claim 1, which comprises a polyalkylene glycol, wherein the relative weight ratio of the polyalkylene oxide to the polyalkylene glycol is within the range of 4.2±

2;

1.

6. The pharmaceutical dosage form according to claim 1, which comprises an antioxidant.

7. The pharmaceutical dosage form according to claim 6, wherein the antioxidant is α

-tocopherol.

8. The pharmaceutical dosage form according to claim 6, wherein the content of the antioxidant is within the range of from 0.001 to 5.0 wt.-%, based on the total weight of the pharmaceutical dosage form.

9. The pharmaceutical dosage form according to claim 1, wherein after storage for 4 weeks at 40°

C. and 75% rel. humidity, the content of opioid (A) amounts to at least 98.0% of its original content before storage.

10. The pharmaceutical dosage form according to claim 1, wherein the opioid (A) is embedded in a matrix comprising the polyalkylene oxide (C), said matrix controlling the release of the opioid from the pharmaceutical dosage form.

11. The pharmaceutical dosage form according to claim 1, wherein the opioid (A) is selected from the group consisting of oxymorphone, oxycodone, hydromorphone, and the physiologically acceptable salts thereof.

12. The pharmaceutical dosage form according to claim 1, wherein the relative weight ratio of the polyalkylene oxide (C) and the opioid (A) is at least 1:

1.

13. The pharmaceutical dosage form according to claim 1, which is adapted for administration once daily or twice daily.

14. The pharmaceutical dosage form according to claim 1, which has a breaking strength of at least 500 N.

15. A packaging containing the pharmaceutical dosage form of claim 1 and an oxygen scavenger.

16. The pharmaceutical dosage form according to claim 7, wherein the content of the antioxidant is within the range of from 0.001 to 5.0 wt.-%, based on the total weight of the pharmaceutical dosage form.