Methods and compositions for deterring abuse of orally administered pharmaceutical products

• US 20080152595A1
• Filed: 12/12/2007
• Published: 06/26/2008
• Est. Priority Date: 11/24/2004
• Status: Abandoned Application

• Current Assignee: Acura Pharmaceuticals Incorporated (Abuse Deterrent Pharma LLC)
• Original Assignee: Acura Pharmaceuticals Incorporated (Abuse Deterrent Pharma LLC)
• Inventors: Leech, Ronald L., Spivey, Ron J., Reddick, Andrew D., Emigh, James F.
• Application Number:
  US12/001,568
• Publication Number:
  US 20080152595A1
• Time in Patent Office: Days
• US Class Current: 424/10.4
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/74 Synthetic polymeric materials
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/2009 Inorganic compounds
• CPC Class Codes: A61K 9/2013 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/205 Polysaccharides, e.g. alginate, gums; Cyclodextrin
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61K 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• 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: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5078 : with drug-free core
• CPC Class Codes: A61K 9/5084 : Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids

Abstract

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.

Claims

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.