Methods and compositions for deterring abuse of opioid containing dosage forms

• US 7,201,920 B2
• Filed: 11/26/2003
• Issued: 04/10/2007
• Est. Priority Date: 11/26/2003
• Status: Active Grant

• Current Assignee: Acura Pharmaceuticals Incorporated (Abuse Deterrent Pharma LLC)
• Original Assignee: Acura Pharmaceuticals Incorporated (Abuse Deterrent Pharma LLC)
• Inventors: Dixon, David, Wadgaonkar, Dilip B., Tewari, Divya, Kumar, Vijai
• Primary Examiner(s): Richter; Johann R.
• Assistant Examiner(s): ALSTRUM ACEVEDO, JAMES HENRY
• Application Number:
  US10/723,654
• Publication Number:
  US 20050112067A1
• Time in Patent Office: 1,231 Days
• Field of Search: 424/451, 424/408, 424/454, 514/282, 514/242, 514/333, 514/277, 514/214.03, 514/766, 514/740, 514/747, 514/764
• US Class Current: 424/454
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• 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 9/2059 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 9/2853 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2893 Tablet coating processes mechanical aspects A61J3/06
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/36 Opioid-abuse

Abstract

This invention relates to an abuse deterrent dosage form of opioid analgesics, wherein an analgesically effective amount of opioid analgesic is combined with a polymer to form a matrix.

Claims

1. A therapeutic pharmaceutical composition comprising

a mixture including

(a) at least one opioid analgesic selected from the group consisting of alfentanil, buprenorphine, butorphanol, carfentanil, codeine, dezocine, diacetylmorphine, dihydrocodeine, dihydromorphine, diprenorphine, etorphine, fentanyl, hydrocodone, hydromorphone, β

-hydroxy-3-methylfentanyl, levo-α

-acetylmethadol, levorphanol, lofentanil, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, pentazocine, pethidine, prepoxyphene, remifentanil, sufentanil, tilidine, tramadol and a pharmaceutically acceptable salt thereof;

(b) gel forming polyethylene oxide at about 3 to 40% by weight;

(c) at least one disintegrant at about 2 to 25% by weight, selected from the group consisting of crospovidone, sodium starch glycolate, and croscarmellose sodium; and

(d) a nasal tissue irritant, wherein the composition functions such that less than about 50% of the total amount of opioid analgesic in the composition is recovered when about 490 mg. of the composition is contacted with 15 ml of water.

2. The therapeutic pharmaceutical composition of claim 1, further comprising an emetic.

3. The therapeutic pharmaceutical composition of claim 1, wherein the gel forming polyethylene oxide has an average molecular weight ranging from about 300,000 to about 5,000,000.

4. The therapeutic pharmaceutical composition of claim 1, wherein the pharmaceutical composition is in unit dose form.

5. The therapeutic pharmaceutical composition of claim 1, wherein the pharmaceutical composition is in a suppository, capsule, caplet, pill, gel, soft gelatin capsule, or compressed tablet form.

6. The therapeutic pharmaceutical composition of claim 1, wherein the analgesic is present in an amount of about 0.5 to about 25 percent by weight.

7. The therapeutic pharmaceutical composition of claim 1, wherein the analgesic is hydrocodone or a pharmaceutically acceptable salt thereof.

8. The therapeutic pharmaceutical composition of claim 1, wherein the analgesic is oxycodone or a pharmaceutically acceptable salt thereof.

9. The therapeutic pharmaceutical composition of claim 8, wherein the disintegrant is crospovidone.

10. The therapeutic pharmaceutical composition of claim 1, wherein the analgesic is morphine or a pharmaceutically acceptable salt thereof.

11. The therapeutic pharmaceutical composition of claim 1, wherein the analgesic is codeine or a pharmaceutically acceptable salt thereof.

12. The therapeutic pharmaceutical composition of claim 1, wherein the analgesic is hydromorphone or a pharmaceutically acceptable salt thereof.

13. The therapeutic pharmaceutical composition of claim 1, wherein the analgesic is propoxyphene or a pharmaceutically acceptable salt thereof.

14. The therapeutic pharmaceutical composition of claim 1, wherein the analgesic is tramadol or a pharmaceutically acceptable salt thereof.

15. The therapeutic pharmaceutical composition of claim 1, wherein the analgesic comprises meperidine or a pharmaceutically acceptable salt thereof.

16. The therapeutic pharmaceutical composition of claim 1, wherein the analgesic is methadone or a pharmaceutically acceptable salt thereof.

17. The therapeutic pharmaceutical composition of claim 1, wherein the analgesic is pentazocine or a pharmaceutically acceptable salt thereof.

18. The therapeutic pharmaceutical composition of claim 1, wherein the disintegrant is crospovidone.

19. A therapeutic pharmaceutical composition comprising

a mixture including

(a) at least one opioid analgesic selected from the group consisting of alfentanil, buprenorphine, butorphanol, carfentanil, codeine, dezocine, diacetylmorphine, dihydrocodeine, dihydromorphine, diprenorphine, etorphine, fentanyl, hydrocodone, hydromorphone, β

-hydroxy-3-methylfentanyl, levo-α

-acetylmethadol, levorphanol, lofentanil, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, pentazocine, pethidine, propoxyphene, remifentanil, sufentanil, tilidine, tramadol and a pharmaceutically acceptable salt, thereof;

(b) gel forming polyethylene oxide at about 3 to 40% by weight;

(c) a surfactant at about 1 to 10% by weight;

(d) at least one disintegrant at about 2 to 25% by weight, wherein the disintegrant is selected from the group consisting of crospovidone, sodium starch glycolate, and croscarmellose sodium; and

(e) wherein the composition functions such that less than about 50% of the total amount of opioid analgesic in the composition is recovered when about 490 mg. of the composition is contacted with 15 ml of water.

20. The therapeutic pharmaceutical composition of claim 19, further comprising an emetic.

21. The therapeutic pharmaceutical composition of claim 19, wherein the gel forming polyethylene oxide has an average molecular weight ranging from about 300,000 to about 5,000,000.

22. The therapeutic pharmaceutical composition of claim 19, wherein the pharmaceutical composition is in unit dose form.

23. The therapeutic pharmaceutical composition of claim 19, wherein the pharmaceutical composition is in a suppository, capsule, caplet, pill, gel, soft gelatin capsule, or compressed tablet form.

24. The therapeutic pharmaceutical composition of claim 19, wherein the analgesic is present in an amount of about 0.5 to about 25 percent by weight.

25. The therapeutic pharmaceutical composition of claim 19, wherein the analgesic is hydrocodone or a pharmaceutically acceptable salt thereof.

26. The therapeutic pharmaceutical composition of claim 19, wherein the analgesic is oxycodone or a pharmaceutically acceptable salt thereof.

27. The therapeutic pharmaceutical composition of claim 26, wherein the disintegrant is crospovidone.

28. The therapeutic pharmaceutical composition of claim 19, wherein the analgesic is morphine or a pharmaceutically acceptable salt thereof.

29. The therapeutic pharmaceutical composition of claim 19, wherein the analgesic is codeine or a pharmaceutically acceptable salt thereof.

30. The therapeutic pharmaceutical composition of claim 19, wherein the analgesic is hydromophone or a pharmaceutically acceptable salt thereof.

31. The therapeutic pharmaceutical composition of claim 19, wherein the analgesic is propoxyphene or a pharmaceutically acceptable salt thereof.

32. The therapeutic pharmaceutical composition of claim 19, wherein the analgesic is tramadol or a pharmaceutically acceptable salt thereof.

33. The therapeutic pharmaceutical composition of claim 19, wherein the analgesic is meperidine or a pharmaceutically acceptable salt thereof.

34. The therapeutic pharmaceutical composition of claim 19, wherein the analgesic is methadone or a pharmaceutically acceptable salt thereof.

35. The therapeutic pharmaceutical composition of claim 19, wherein the analgesic is pentazocine or a pharmaceutically acceptable salt thereof.

36. The therapeutic pharmaceutical composition of claim 19, wherein the disintegrant is crospovidone.

37. A therapeutic pharmaceutical composition comprising:

a mixture including

(a) at least one opioid analgesic selected from the group consisting of alfentanil, buprenorphine, butorphanol, carfentanil, codeine, dezocine, diacetylmorphine, dihydrocodeine, dihydromorphine, diprenorphine, etorphine, fentanyl, hydrocodone, hydromorphone, β

-hydroxy-3-methylfentanyl, levo-α

-acetylmethadol, levorphanol, lofentanil, meperidine, methadone, morphine, nalbuphine, oxycodone, oxymorphone, pentazocine, pethidine, propoxyphene, remifentanil, sufentanil, tilidine, tramadol and a pharmaceutically acceptable salt thereof;

(b) gel forming polyethylene oxide at about 3 to about 40 percent by weight;

(c) at least one disintegrant at about 2 to 25 percent by weight wherein the disintegrant is selected from the group consisting of crospovidone, sodium starch glycolate, and croscarmellose sodium; and

(d) sodium lauryl sulfate at about 1 to 10 percent by weight.

38. The therapeutic pharmaceutical composition of claim 37, further comprising an emetic.

39. The therapeutic pharmaceutical composition of claim 37, wherein the gel forming polyethylene oxide has an average molecular weight ranging from about 300,000 to about 5,000,000.

40. The therapeutic pharmaceutical composition of claim 37, wherein the pharmaceutical composition is in unit dose form.

41. The therapeutic pharmaceutical composition of claim 37, wherein the pharmaceutical composition is in a suppository, capsule, caplet, pill, gel, soft gelatin capsule, or compressed tablet form.

42. The therapeutic pharmaceutical composition of claim 37, wherein the analgesic is present in an amount of about 0.5 to about 25 percent by weight.

43. The therapeutic pharmaceutical composition of claim 37, wherein the analgesic is hydrocodone or a pharmaceutically acceptable salt thereof.

44. The therapeutic pharmaceutical composition of claim 37, wherein the analgesic is oxycodone or a pharmaceutically acceptable salt thereof.

45. The therapeutic pharmaceutical composition of claim 44, wherein the disintegrant is crospovidone.

46. The therapeutic pharmaceutical composition of claim 37, wherein the analgesic is morphine or a pharmaceutically acceptable salt thereof.

47. The therapeutic pharmaceutical composition of claim 37, wherein the analgesic is codeine or a pharmaceutically acceptable salt thereof.

48. The therapeutic pharmaceutical composition of claim 37, wherein the analgesic is hydromorphone or a pharmaceutically acceptable salt thereof.

49. The therapeutic pharmaceutical composition of claim 37, wherein the analgesic is propoxyphene or a pharmaceutically acceptable salt thereof.

50. The therapeutic pharmaceutical composition of claim 37, wherein the analgesic is tramadol or a pharmaceutically acceptable salt thereof.

51. The therapeutic pharmaceutical composition of claim 37, wherein the analgesic is meperidine or a pharmaceutically acceptable salt thereof.

52. The therapeutic pharmaceutical composition of claim 37, wherein the analgesic is methadone or a pharmaceutically acceptable salt thereof.

53. The therapeutic pharmaceutical composition of claim 37, wherein the analgesic is pentazocine or a pharmaceutically acceptable salt thereof.

54. The therapeutic pharmaceutical composition of claim 37, wherein the disintegrant is crospovidone.