Sequestering subunit and related compositions and methods
View Patent ↗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.
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.