SEQUESTERING SUBUNIT AND RELATED COMPOSITIONS AND METHODS
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 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 - 38 . (canceled)
39 . A method for manufacturing a pharmaceutical composition comprising a sequestering subunit, the method comprising admixing a substrate, naltrexone, and a first hydrophobic material to form a naltrexone core, and coating the naltrexone core with a blocking agent comprising a second hydrophobic material and a surfactant.
40 . The method of claim 39 wherein the first hydrophobic material is different from the second hydrophobic material.
41 . The method of claim 39 wherein the first hydrophobic material is Methocel E5P.
42 . The method of claim 39 wherein the second hydrophobic material is a copolymer of acrylic acid and methacrylic acid.
43 . The method of claim 42 wherein the second hydrophobic material is Eudragit RSPO.
44 . The method of claim 39 wherein the surfactant is sodium lauryl sulphate.
45 . The method of claim 39 wherein the ratio of the second hydrophobic material to surfactant is about 30:1.
46 . The method of claim 39 wherein the blocking agent is applied to about a 16-20% weight gain of the naltrexone core.
47 . The method of claim 39 further comprising overcoating the sequestering subunit with a releasable opioid agonist.
48 . The method of claim 47 wherein the therapeutic agent is in immediate release form.
49 . The method of claim 47 wherein the therapeutic agent is in sustained release form.
50 . The method of any one of claim 47 , 48 , or 49 wherein the opioid agonist is selected from the group consisting of morphine, hydromorphone, oxycodone, and hydrocodone.
51 . The method of claim 47 wherein the opioid agonist is morphine.
52 . The method of claim 39 wherein the substrate is a sugar sphere.
53 . The method of claim 45 wherein the second hydrophobic material is a copolymer of acrylic acid and methacrylic acid.
54 . The method of claim 53 wherein the second hydrophobic material is Eudragit RSPO.
55 . The method of claim 53 wherein the surfactant is sodium lauryl sulphate.
56 . The method of claim 53 wherein the second hydrophobic material is a copolymer of acrylic acid and methacrylic acid and the surfactant is sodium lauryl sulphate.
57 . The method of claim 53 wherein the second hydrophobic material is Eudragit RSPO and the surfactant is sodium lauryl sulphate.
58 . The method of claim 56 wherein the wherein the opioid agonist is selected from the group consisting of morphine, hydromorphone, oxycodone, and hydrocodone.
59 . The method of claim 58 wherein the opioid agonist is morphine.
60 . The method of claim 57 wherein the wherein the opioid agonist is selected from the group consisting of morphine, hydromorphone, oxycodone, and hydrocodone.
61 . The method of claim 60 wherein the opioid agonist is morphine.
62 . A method for manufacturing a pharmaceutical composition comprising a sequestering subunit, the method comprising mixing naltrexone and a first hydrophobic material to form a solution, layering the solution onto a sugar sphere to form a naltrexone core, and coating the naltrexone core with a blocking agent comprising a second hydrophobic material and a surfactant.
63 . The method of claim 62 wherein the solution is layered onto the sugar sphere in a fluid-bed.
64 . The method of claim 62 wherein the first hydrophobic material is different from the second hydrophobic material.
65 . The method of claim 62 wherein the first hydrophobic material is Methocel ESP.
66 . The method of claim 62 wherein the second hydrophobic material is a copolymer of acrylic acid and methacrylic acid.
67 . The method of claim 62 wherein the second hydrophobic material is Eudragit RSPO.
68 . The method of claim 62 wherein the surfactant is sodium lauryl sulphate.
69 . The method of claim 62 wherein the ratio of the second hydrophobic material to surfactant is about 30:1.
70 . The method of claim 62 wherein the blocking agent is applied onto the naltrexone core to about a 16-20% weight gain of the naltrexone core.
71 . The method of any one of claims 62 further comprising overcoating the sequestering subunit with a releasable opioid agonist.
72 . The method of claim 71 wherein the therapeutic agent is in immediate release form.
73 . The method of claim 71 wherein the therapeutic agent is in sustained release form.
74 . The method of any one of claim 71 , 72 , or 73 wherein the opioid agonist is selected from the group consisting of morphine, hydromorphone, oxycodone, and hydrocodone.
75 . The method of claim 71 wherein the opioid agonist is morphine.
76 . The method of claim 69 wherein the second hydrophobic material is a copolymer of acrylic acid and methacrylic acid.
77 . The method of claim 76 wherein the second hydrophobic material is Eudragit RSPO.
78 . The method of claim 69 wherein the surfactant is sodium lauryl sulphate.
79 . The method of claim 69 wherein the second hydrophobic material is a copolymer of acrylic acid and methacrylic acid and the surfactant is sodium lauryl sulphate.
80 . The method of claim 69 wherein the second hydrophobic material is Eudragit RSPO and the surfactant is sodium lauryl sulphate.
81 . The method of claim 79 wherein the wherein the opioid agonist is selected from the group consisting of morphine, hydromorphone, oxycodone, and hydrocodone.
82 . The method of claim 81 wherein the opioid agonist is morphine.
83 . The method of claim 80 wherein the wherein the opioid agonist is selected from the group consisting of morphine, hydromorphone, oxycodone, and hydrocodone.
84 . The method of claim 83 wherein the opioid agonist is morphine.