Sequestering subunit and related compositions and methods

• US 7,815,934 B2
• Filed: 09/22/2003
• Issued: 10/19/2010
• Est. Priority Date: 09/20/2002
• Status: Expired due to Fees

• Current Assignee: Alpharma Pharmaceuticals LLC (Pfizer Inc.)
• Original Assignee: Alpharma Pharmaceuticals LLC (Pfizer Inc.)
• Inventors: Boehm, Garth
• Primary Examiner(s): Azpuru; Carlos A
• Application Number:
  US10/667,676
• Publication Number:
  US 20040131552A1
• Time in Patent Office: 2,584 Days
• Field of Search: None
• US Class Current: 424/451
• CPC Class Codes: A61K 9/2077 Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
• CPC Class Codes: A61K 9/209 containing drug in at least two layers or in the core and in at least one outer layer
• CPC Class Codes: A61K 9/5078 with drug-free core
• 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

A sequestering subunit comprising an aversive agent and a blocking agent, wherein the blocking agent substantially prevents release of the aversive agent from the sequestering subunit in the gastrointestinal tract for a time period that is greater than 24 hours; a composition comprising a sequestering subunit and a therapeutic agent in releasable form, wherein, optionally, the mechanical fragility of the sequestering subunit is the same as the mechanical fragility of the therapeutic agent in releasable form; a capsule or tablet comprising a sequestering subunit and a therapeutic agent; and a method of preventing abuse of a therapeutic agent.

Claims

1. A pharmaceutical composition comprising a sequestering subunit comprising naltrexone or a pharmaceutically acceptable salt thereof and a blocking agent comprising a surfactant, wherein the blocking agent substantially prevents release of the naltrexone or a pharmaceutically acceptable salt thereof from the sequestering subunit and the sequestering subunit is overcoated with an opioid agonist or a pharmaceutically acceptable salt thereof in releasable form.

2. The pharmaceutical composition of claim 1 wherein the blocking agent prevents the release of at least about 99% of the naltrexone or a pharmaceutically acceptable salt thereof from the sequestering subunit in the gastrointestinal tract for at least about 12 hours.

3. The pharmaceutical composition of claim 1 wherein the blocking agent prevents the release of at least about 95% of the naltrexone or a pharmaceutically acceptable salt thereof from the sequestering subunit in the gastrointestinal tract for a time period that is greater than 24 hours.

4. The pharmaceutical composition of claim 1 wherein the opioid agonist is selected from the group consisting of morphine, hydromorphone, oxycodone, hydrocodone, and pharmaceutically acceptable salts thereof.

5. The pharmaceutical composition of claim 4 wherein the opioid agonist is morphine or a pharmaceutically acceptable salt thereof.

6. The pharmaceutical composition of claim 1 wherein the surfactant is sodium lauryl sulphate.

7. The pharmaceutical composition of claim 1 wherein the blocking agent comprises Eudragit RS PO and sodium lauryl sulphate, the blocking agent prevents the release of at least about 99% of the naltrexone or a pharmaceutically acceptable salt thereof from the sequestering subunit in the gastrointestinal tract for at least about 12 hours, the blocking agent prevents the release of at least about 95% of the naltrexone or a pharmaceutically acceptable salt thereof from the sequestering subunit in the gastrointestinal tract for a time period that is greater than 24 hours, and the opioid agonist is morphine or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition comprising:

a. a sequestering subunit comprising;

i. a naltrexone core comprising naltrexone or a pharmaceutically acceptable salt thereof on a substrate; and

,

ii. a coating comprising a hydrophobic material and a surfactant covering the naltrexone core; and

,

b. an overcoat comprising an opioid agonist or a pharmaceutically acceptable salt thereof covering the sequestering subunit.

9. The pharmaceutical composition of claim 8 wherein the substrate is a spheroid or a bead.

10. The pharmaceutical composition of claim 8 wherein the surfactant is sodium lauryl sulphate.

11. The pharmaceutical composition of claim 8 wherein the coating prevents the release of at least about 99% of the naltrexone or a pharmaceutically acceptable salt thereof from the sequestering subunit in the gastrointestinal tract for at least about 12 hours.

12. The pharmaceutical composition of claim 8 wherein the coating prevents the release of at least about 95% of the naltrexone or a pharmaceutically acceptable salt thereof from the sequestering subunit in the gastrointestinal tract for a time period that is greater than 24 hours.

13. The pharmaceutical composition of claim 8 wherein the opioid agonist is selected from the group consisting of morphine, hydromorphone, oxycodone, hydrocodone, and pharmaceutically acceptable salts thereof.

14. The pharmaceutical composition of claim 13 wherein the opioid agonist is morphine or a pharmaceutically acceptable salt thereof.

15. The pharmaceutical composition of claim 8 wherein the blocking agent comprises Eudragit RS PO and sodium lauryl sulphate, the blocking agent prevents the release of at least about 99% of the naltrexone or a pharmaceutically acceptable salt thereof from the sequestering subunit in the gastrointestinal tract for at least about 12 hours, the blocking agent prevents the release of at least about 95% of the naltrexone or a pharmaceutically acceptable salt thereof from the sequestering subunit in the gastrointestinal tract for a time period that is greater than 24 hours, and the opioid agonist is morphine or a pharmaceutically acceptable salt thereof.

16. A sequestering subunit comprising naltrexone or a pharmaceutically acceptable salt thereof and a blocking agent comprising a surfactant wherein the blocking agent prevents the release of at least about 99% of the naltrexone or a pharmaceutically acceptable salt thereof from the sequestering subunit in the gastrointestinal tract for at least about 12 hours and prevents the release of at least about 95% of the naltrexone or a pharmaceutically acceptable salt thereof from the sequestering subunit in the gastrointestinal tract for a time period that is greater than 24 hours.

17. The sequestering subunit of claim 16 wherein the surfactant is sodium lauryl sulphate.

18. The sequestering subunit of claim 16 wherein the blocking agent comprises the surfactant sodium lauryl sulphate and Eudragit RS PO.