Tamper resistant immediate release capsule formulation comprising tapentadol

• US 9,913,814 B2
• Filed: 09/07/2016
• Issued: 03/13/2018
• Est. Priority Date: 05/12/2014
• Status: Expired due to Fees

• Current Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Original Assignee: Grunenthal GMBH (Grünenthal Pharma GmbH & Co. KG)
• Inventors: Friedrich, Ingo, Fuhrherr, Richard, Mschter, Silke, Wengner, Simone
• Primary Examiner(s): GULLEDGE, BRIAN M
• Application Number:
  US15/257,972
• Publication Number:
  US 20160374965A1
• Time in Patent Office: 552 Days
• Field of Search: None
• CPC Class Codes: A61K 31/137 Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61K 9/485 Inorganic compounds
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/36 Opioid-abuse
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

The invention is directed to an immediate release capsule which mitigates the abuse of Tapentadol or physiologically acceptable salt thereof by direct intravenous injection. The capsule comprises a tamper resistant formulation which when mixed with water and heated, results in a turbid, bubbling mixture that is not injectable with a standard insulin syringe.

Claims

1. A tamper resistant pharmaceutical capsule comprising a capsule filling and a capsule shell, wherein said capsule filling is encapsulated by said capsule shell and comprises:

(a) Tapentadol or a physiologically acceptable salt thereof in an amount within the range of from 10 mg to 400 mg, as equivalent weight relative to Tapentadol free base; and

(b) a liquid excipient blend comprising a solvent, a surfactant, and a viscosity enhancer;

wherein the viscosity enhancer comprises colloidal anhydrous silica and a gum;

wherein a mixture of 250 milligrams of the liquid excipient blend with 5 milliliters of water at the mixture'"'"'s boiling point forms a viscous phase which cannot pass through a 25 millimeter long needle having an inner diameter of 0.60 millimeters; and

wherein the capsule provides immediate release of Tapentadol or the physiologically acceptable salt thereof upon oral administration.

2. The capsule according to claim 1, wherein the gum is selected from the group consisting of acacia, agar, tragacanth, guar gum, xanthan gum, locust bean gum, tara gum, karaya, gellan gum, welan gum, and rhamsan gum.

3. The capsule according to claim 1, wherein the total content of viscosity enhancer is within the range of from 0.1 to 10 wt.-%, relative to the total weight of the capsule filling.

4. The capsule according to claim 1, wherein the total content of solvent is within the range of from 10 to 90 wt.-%, relative to the total weight of the capsule filling.

5. The capsule according to claim 1, wherein the liquid excipient blend comprises an ion exchange resin.

6. The capsule according to claim 5, wherein the ion exchange resin is anionic.

7. The capsule according to claim 5, wherein the total content of ion exchange resin is within the range of from 0.1 to 25 wt.-%, relative to the total weight of the capsule filling.

8. The capsule according to claim 1, wherein the surfactant is nonionic.

9. The capsule according to claim 8, wherein the nonionic surfactant is selected from the group consisting of glycerol monoesters with C_6-18-fatty acids, glycerol diesters with identical or different C_6-18-fatty acids, glycerol triesters with identical or different C_{6 -18}-fatty acids, polyethylene glycol monoesters with C_6-18-fatty acids, polyethylene glycol diesters with identical or different C_6-18-fatty acids, and mixtures of any of the foregoing.

10. The capsule according to claim 1, wherein the total content of surfactant is within the range of from 0.1 to 35 wt.-%, relative to the total weight of the capsule filling.

11. The capsule according to claim 1, wherein the total content of Tapentadol or physiologically acceptable salt thereof, as equivalent weight relative to Tapentadol free base, is within the range of from 0.1 to 25 wt.-%, relative to the total weight of the capsule filling.

12. A method for treating pain in a patient in need of such treatment, said method comprising administering to said patient at least one capsule according to claim 1.

13. A method for preventing parenteral abuse of Tapentadol or a physiologically acceptable salt thereof, said method comprising providing the Tapentadol or a physiologically acceptable salt thereof in the form of a capsule according to claim 1.