Methods and compositions for deterring abuse of orally administered pharmaceutical products
This invention relates to an abuse deterrent formulation of an oral dosage form of a therapeutically effective amount of any active drug substance that can be subject to abuse combined with a gel forming polymer, a nasal mucosal irritating surfactant and a flushing agent. Such a dosage form is intended to deter abuse of the active drug substance via injection, nasal inhalation or consumption of quantities of the dosage unit exceeding the usual therapeutically effective dose.
1 . A therapeutic pharmaceutical composite having at least two immediate release sequestered subunits, comprising:
(a) a first immediate release sequestered subunit comprising a mixture of: a gel forming polymer; a nasal tissue irritant; and a disintegrant; and
(b) a second immediate release sequestered subunit comprising an opioid analgesic.
2 . The therapeutic pharmaceutical composite of claim 1 , wherein the first and second immediate release sequestered subunits are indistinguishable in size, shape, and color.
3 . The therapeutic pharmaceutical composite of claim 1 , further comprising a third sequestered subunit, wherein the third sequestered subunit comprises an extended release subunit.
4 . The therapeutic pharmaceutical composite of claim 3 , wherein the immediate and extended release sequestered subunits are indistinguishable in size, shape, and color.
5 . The therapeutic pharmaceutical composite of claim 1 , wherein the therapeutic pharmaceutical composite is in unit dose form.
6 . The therapeutic pharmaceutical composite of claim 1 , wherein the therapeutic pharmaceutical composite is in a suppository, capsule, caplet, pill, gel, soft gelatin capsule, or compressed tablet form.
7 . The therapeutic pharmaceutical composite of claim 1 , wherein the gel forming polymer comprises one or more of polyethylene oxide, polyvinyl alcohol, hydroxypropyl methyl cellulose and a carbomer.
8 . The therapeutic pharmaceutical composite of claim 7 , wherein the gel forming polymer is present in an amount of about 3 to about 40 percent by weight.
9 . The therapeutic pharmaceutical composite of claim 7 , wherein the gel forming polymer has an average molecular weight ranging from about 300,000 to about 5,000,000.
10 . The therapeutic pharmaceutical composite of claim 1 , wherein the nasal tissue irritant is selected from the group consisting of: poloxamer, sorbitan monoesters, glyceryl monooleates, and sodium lauryl sulfate.
11 . The therapeutic pharmaceutical composite of claim 10 , wherein the nasal tissue irritant is sodium lauryl sulfate at about 1 to about 10 percent by weight.
12 . The therapeutic pharmaceutical composite of claim 1 , wherein the disintegrant is selected from the group consisting of: crosprovidone, sodium starch glycolate, and croscarmellose sodium.
13 . The therapeutic pharmaceutical composite of claim 12 , wherein the disintegrant is present in an amount of about 2 to about 25 percent by weight.
14 . The therapeutic pharmaceutical composite of claim 1 , wherein the opioid analgesic is present in an amount of about 0.5 to about 25 percent by weight.
15 . The therapeutic pharmaceutical composite of claim 1 , wherein the opioid analgesic comprises hydrocodone or a therapeutically acceptable salt thereof.
16 . The therapeutic pharmaceutical composite of claim 1 , wherein the opioid analgesic comprises oxycodone or a therapeutically acceptable salt thereof.
17 . The therapeutic pharmaceutical composite of claim 1 , wherein the opioid analgesic comprises morphine or a therapeutically acceptable salt thereof.
18 . The therapeutic pharmaceutical composite of claim 1 , wherein the opioid analgesic is selected from the group consisting of: alfentanil, amphetamines, buprenorphine, butorphanol, carfentanil, codeine, dihydromorphine, diphenoxylate, diprenorphine, etorphine, fentanyl, hydrocodone, hydromorphone, β-hydroxy-3-methylfentanyl, levo-α-acetylmethadol, levorphanol, lofentanil, meperidine, methadone, methylphenidate, morphine, nalbuphine, nalmefene, o-methylnatrexone, naloxone, naltrexone, oxycodone, oxymorphone, pentazocine, pethidine, propoxyphene, remifentanil, sufentanil, tilidine and tramodol, or therapeutically acceptable salts thereof.
19 . A method of making a therapeutic pharmaceutical composite suitable for deterring drug abuse comprising:
(a) providing a first immediate release sequestered subunit comprising a mixture of: a gel forming polymer, a nasal tissue irritant, and a disintegrant, by:
i. controlling the molecular weight or viscosity of the gel forming polymer;
ii. controlling the amount of nasal tissue irritant such that nasal tissue irritation occurs if inhaled; and
iii. controlling the percentage by weight of disintegrant;
(b) providing a second immediate release sequestered subunit comprising a drug susceptible to abuse; and
(c) combining the first and second immediate release sequestered subunits to form a therapeutic pharmaceutical composite;
wherein the therapeutic pharmaceutical composite deters abuse by forming a viscous gel upon contact with a solvent and inducing nasal irritation if inhaled.
20 . The method of claim 19 , wherein the first and second immediate release sequestered subunits are indistinguishable in size, shape, and color.
21 . The method of claim 19 , further providing a third sequestered subunit, wherein the third sequestered subunit comprises an extended release subunit.
22 . The method of claim 21 , wherein the immediate and extended release sequestered subunits are indistinguishable in size, shape, and color.
23 . The method of claim 19 , further comprising the step of processing the therapeutic pharmaceutical composite into a unit dose form.
24 . The method of claim 19 , further comprising the step of processing the therapeutic pharmaceutical composite into a suppository, capsule, caplet, pill, or a direct compressed tablet form.
25 . The method of claim 19 , wherein the subunits are sequestered within a therapeutic pharmaceutical composite.
26 . The method of claim 19 , wherein the gel forming polymer comprises one or more of polyethylene oxide, polyvinyl alcohol, hydroxypropyl methyl cellulose and a carbomer.
27 . The method of claim 26 , wherein the gel forming polymer is present in an amount of about 3 to about 40 percent by weight.
28 . The method of claim 26 , wherein the gel forming polymer has an average molecular weight ranging from about 300,000 to about 5,000,000.
29 . The method of claim 19 , wherein the nasal tissue irritant is selected from the group consisting of: poloxamer, sorbitan monoesters, glyceryl monooleates, and sodium lauryl sulfate.
30 . The method of claim 29 , wherein the nasal tissue irritant is sodium lauryl sulfate at about 1 to about 10 percent by weight.
31 . The method of claim 19 , wherein the disintegrant is selected from the group consisting of: crosprovidone, sodium starch glycolate, and croscarmellose sodium.
32 . The method of claim 31 , wherein the disintegrant is present in an amount of about 2 to about 25 percent by weight.
33 . The method of claim 19 , wherein the drug susceptible to abuse is an opioid analgesic.
34 . The method of claim 33 , wherein the opioid analgesic is present in an amount of about 0.5 to about 25 percent by weight.
35 . The method of claim 33 , wherein the opioid analgesic comprises hydrocodone or a therapeutically acceptable salt thereof.
36 . The method of claim 33 , wherein the opioid analgesic comprises oxycodone or a therapeutically acceptable salt thereof.
37 . The method of claim 33 , wherein the opioid analgesic comprises morphine or a therapeutically acceptable salt thereof.
38 . The method of claim 33 , wherein the opioid analgesic is selected from the group consisting of: alfentanil, amphetamines, buprenorphine, butorphanol, carfentanil, codeine, dihydromorphine, diphenoxylate, diprenorphine, etorphine, fentanyl, hydrocodone, hydromorphone, β-hydroxy-3-methylfentanyl, levo-α-acetylmethadol, levorphanol, lofentanil, meperidine, methadone, methylphenidate, morphine, nalbuphine, nalmefene, o-methylnatrexone, naloxone, naltrexone, oxycodone, oxymorphone, pentazocine, pethidine, propoxyphene, remifentanil, sufentanil, tilidine and tramodol, or therapeutically acceptable salts thereof.
39 . A sequestered pharmaceutical composition subunit comprising:
(a) a gel forming polymer;
(b) a nasal tissue irritant; and
(c) a disintegrant.
40 . The sequestered pharmaceutical composition subunit of claim 39 , wherein the gel forming polymer comprises one or more of polyethylene oxide, polyvinyl alcohol, hydroxypropyl methyl cellulose and a carbomer.
41 . The sequestered pharmaceutical composition subunit of claim 40 , wherein the gel forming polymer is present in an amount of about 3 to about 40 percent by weight.
42 . The sequestered pharmaceutical composition subunit of claim 40 , wherein the gel forming polymer has an average molecular weight ranging from about 300,000 to about 5,000,000.
43 . The sequestered pharmaceutical composition subunit of claim 39 , wherein the nasal tissue irritant is selected from the group consisting of: poloxamer, sorbitan monoesters, glyceryl monooleates, and sodium lauryl sulfate.
44 . The sequestered pharmaceutical composition subunit of claim 43 , wherein the nasal tissue irritant is sodium lauryl sulfate at about 1 to about 10 percent by weight.
45 . The sequestered pharmaceutical composition subunit of claim 39 , wherein the disintegrant is selected from the group consisting of: crosprovidone, sodium starch glycolate, and croscarmellose sodium.
46 . The sequestered pharmaceutical composition subunit of claim 45 , wherein the disintegrant is present in an amount of about 2 to about 25 percent by weight.
47 . The sequestered pharmaceutical composition subunit of claim 39 , comprising:
(a) polyethylene oxide in an amount of about 3 to about 40 percent by weight;
(b) sodium lauryl sulfate in an amount of about 1 to about 10 percent by weight; and
(c) crosprovidone in an amount of about 2 to about 25 percent by weight.