Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc

• US 10,064,945 B2
• Filed: 05/10/2013
• Issued: 09/04/2018
• Est. Priority Date: 05/11/2012
• Status: Expired due to Fees

• Current Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Original Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Inventors: Barnscheid, Lutz, Galia, Eric, Geissler, Anja, Patz, Jana, Schwier, Sebastian, Baronsky-Probst, Julia
• Primary Examiner(s): Rosenthal, Andrew S
• Application Number:
  US13/891,306
• Publication Number:
  US 20130303623A1
• Time in Patent Office: 1,943 Days
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• 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

Abstract

A thermoformed, tamper-resistant pharmaceutical dosage form comprises:

• a) a pharmacologically active ingredient;
• b) a polyalkylene oxide having a weight average molecular weight of more than 200,000 g/mol; and
• c) a zinc component, wherein the content of said zinc component is at least 1 ppm, relative to the total weight of the pharmaceutical dosage form.

When the pharmacologically active ingredient is effective against pain, the pharmaceutical dosage form may be used in a method of treating pain. When the pharmacologically active ingredient has abuse potential, the pharmaceutical dosage form may be used in a method of reducing the incidence of the abuse of said pharmacologically active ingredient.

Claims

1. A thermoformed, tamper-resistant pharmaceutical dosage form comprising:

a) a pharmacologically active ingredient selected from the group consisting of opioids, stimulants, tranquilizers, and narcotics;

b) a polyalkylene oxide having a weight average molecular weight of more than 200,000 g/mol;

c) a zinc component, wherein said zinc component has a zinc content of at most 1,000 ppm, relative to a total weight of the dosage form; and

d) an antioxidant.

2. The pharmaceutical dosage form according to claim 1, wherein the polyalkylene oxide is obtainable by polymerizing alkylene oxide in presence of the zinc component.

3. The pharmaceutical dosage form according to claim 1, wherein an aqueous dispersion of the pure polyalkylene oxide composition in pure water at 25°

C. and at a concentration of 1 wt.-% has a pH value of at most 7.7.

4. The pharmaceutical dosage form according to claim 1, wherein the zinc content of said zinc component is at least 10 ppm relative to the total weight of the polyalkylene oxide composition.

5. The pharmaceutical dosage form according to claim 1, which has a breaking strength of at least 300 N.

6. The pharmaceutical dosage form according to claim 1, wherein the pharmacologically active ingredient is an opioid.

7. The pharmaceutical dosage form according to claim 1, wherein the pharmacologically active ingredient is embedded in a controlled-release matrix comprising the polyalkylene oxide and the zinc component.

8. The pharmaceutical dosage form according to claim 1, which is monolithic or multiparticulate.

9. The pharmaceutical dosage form according to claim 1, which is melt-extruded.

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

11. A process for the manufacture of a pharmaceutical dosage form according to claim 1 comprising the steps of:

(a) mixing the pharmacologically active ingredient, the polyalkylene oxide composition, the zinc component, and the antioxidant, and optionally present excipients to obtain a mixture; and

(b) press-forming the mixture obtained in step (a) with preceding, simultaneous, or subsequent exposure to heat.

12. The process according to claim 11, wherein step (b) is performed by means of an extruder.

13. A pharmaceutical dosage form obtainable by the process of claim 12.

14. A method of treating pain in a patient in need thereof, said method comprising administering to said patient a pharmaceutical dosage form according to claim 1, said pharmaceutical dosage form comprising a pharmacologically active ingredient effective to treat pain.

15. A method of reducing the incidence of drug abuse of a pharmacologically active ingredient with abuse potential, said method comprising providing said pharmacologically active ingredient in the form of a pharmaceutical dosage form according to claim 1.

16. The pharmaceutical dosage form according to claim 1, which does not comprise zinc sulfate or zinc stearate.

17. The pharmaceutical dosage form according to claim 1, wherein the content of said zinc component is at least 1 ppm relative to the total weight of the pharmaceutical dosage form.

18. The pharmaceutical dosage from according to claim 1, wherein the antioxidant is selected from the group consisting of butylhydroxytoluene, butylhydroxyanisole and α

-tocopherol.

19. The pharmaceutical dosage form according to claim 1, wherein the pharmacologically active ingredient is oxycodone or a physiologically acceptable salt thereof.

20. The pharmaceutical dosage form according to claim 1, wherein the pharmacologically active ingredient is oxymorphone or a physiologically acceptable salt thereof.

21. The pharmaceutical dosage form according to claim 1, wherein the pharmacologically active ingredient is hydrocodone or a physiologically acceptable salt thereof.

22. The pharmaceutical dosage form according to claim 1, wherein the pharmacologically active ingredient is hydromorphone or a physiologically acceptable salt thereof.

23. The pharmaceutical dosage form according to claim 1, wherein the pharmacologically active ingredient is morphine or a physiologically acceptable salt thereof.

24. The pharmaceutical dosage form according to claim 1, wherein the pharmacologically active ingredient is tapentadol or a physiologically acceptable salt thereof.

25. The pharmaceutical dosage form according to claim 1, wherein the pharmacologically active ingredient is amphetamine or a physiologically acceptable salt thereof.

26. The pharmaceutical dosage form according to claim 1, wherein the pharmacologically active ingredient is amphetaminil or a physiologically acceptable salt thereof.

27. The pharmaceutical dosage form according to claim 1, wherein the pharmacologically active ingredient is methamphetamine or a physiologically acceptable salt thereof.

28. The pharmaceutical dosage form according to claim 1, wherein the pharmacologically active ingredient is methylphenidate or a physiologically acceptable salt thereof.