Combination of tramadol and substances that comprise gabapentin

• US 20060257484A1
• Filed: 04/13/2006
• Published: 11/16/2006
• Est. Priority Date: 04/19/2005
• Status: Abandoned Application

• Current Assignee: ALZA Corporation (Johnson & Johnson), Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson), Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: Abraham, David, Wong, Patrick S.L., Hwang, Stephen S., Yan, Dong, Chaplan, Sandra
• Application Number:
  US11/404,293
• Publication Number:
  US 20060257484A1
• Time in Patent Office: Days
• US Class Current: 424/473
• 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 31/135 having aromatic rings , e.g. ketamine, nortriptyline methadone A61K31/137
• CPC Class Codes: A61K 31/14 Quaternary ammonium compounds, e.g. edrophonium, choline betaines A61K31/205
• CPC Class Codes: A61K 31/197 the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid carnitine A61K31/205
• CPC Class Codes: A61K 31/35 having six-membered rings with one oxygen as the only ring hetero atom
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids

Abstract

Disclosed are substances, compositions, dosage forms and methods that comprise tramadol and substances that comprise gabapentin.

Claims

1. An oral dosage form comprising:

an oral controlled delivery dosing structure comprising structure that controllably delivers tramadol and a substance that comprises gabapentin; and

wherein the weight ratio of gabapentin equivalent to tramadol equivalentpresent in the oral dosage form ranges from about 0.75;

1 to about 6.5;

1; and

wherein the total weight of the tramadol and substance that comprises gabapentin present in the oral dosage form is less than about 1500 milligrams; and

wherein the oral controlled delivery dosing structure is adapted to controllably deliver the substance that comprises gabapentin at a rate that is effective to, after a single administration of the oral dosage form to a patient, maintain a gabapentin plasma drug concentration that is at least about twenty-five percent of a gabapentin Cmax throughout a window of at least about fifteen hours duration after a time at which the gabapentin Cmax occurs.

2. The oral dosage form of claim 1, wherein the tramadol comprises tramnadol HCl.

3. The oral dosage form of claim 1, wherein the substance that comprises gabapentin comprises a complex that comprises gabapentin and an alkyl sulfate salt.

4. The oral dosage form of claim 1, wherein the window is of at least about eighteen hours duration after the time at which the gabapentin Cmax occurs.

5. The oral dosage form of claim 1, wherein the weight ratio of gabapentin equivalent to tramadol equivalent present in the oral dosage form ranges from about 0.80:

1 to about 5.5;

1.

6. The oral dosage form of claim 1, wherein the oral dosage form comprises an osmotic oral dosage form.

52. A method comprising

(1) providing the oral dosage form of claim 43;

and

(2) administering the oral dosage form to a patient.

53. The method of claim 52, wherein the oral dosage form comprises an oral controlled delivery dosage form.

54. The method of claim 53, wherein the oral dosage form comprises an osmotic oral controlled delivery dosage form.

55. The method of claim 54, wherein the osmotic oral controlled delivery dosage form comprises a solid osmotic oral controlled delivery dosage form.

56. The method of claim 54, wherein the osmotic oral controlled delivery dosage form comprises a liquid osmotic oral controlled delivery dosage form.

7. An oral dosage form comprising:

an oral controlled delivery dosing structure comprising structure that controllably delivers tramadol and a substance that comprises gabapentin;

wherein the weight ratio of gabapentin equivalent to tramadol equivalent present in the oral dosage form ranges from about 0.75;

1 to about 6.5;

1; and

wherein the total weight of the tramadol and substance that comprises gabapentin present in the oral dosage form is less than about 1500 milligrams; and

wherein the controlled delivery dosing structure is adapted to controllably deliver the substance that comprises gabapentin contained by the controlled delivery dosing structure in a delivery dose pattern of from about 0 wt % to about 20 wt % in about 0 to about 4 hrs, about 20 wt % to about 50 wt % in about 0 to about 8 hrs, about 55 wt % to about 85 wt % in about 0 to about 14 hrs, and about 80 wt % to about 100 wt % in about 0 to about 24 hrs, wherein the wt % is based on the total weight of the substance that comprises gabapentin present in the controlled delivery dosage form.

8. The oral dosage form of claim 7, wherein the tramadol comprises trarnadol HCl.

9. The oral dosage form of claim 7, wherein the substance that comprises gabapentin comprises a complex that comprises gabapentin and an alkyl sulfate salt.

10. The oral dosage form of claim 7, wherein the weight ratio of gabapentin equivalent to tramadol equivalent present in the oral dosage form ranges from about 0.80:

1 to about 5.5;

1.

11. The oral dosage form of claim 7, wherein the oral dosage form comprises an osmotic oral dosage form.

12. An oral dosage form comprising:

an oral controlled delivery dosing structure comprising structure that controllably delivers tramadol and a substance that comprises gabapentin;

wherein the weight ratio of gabapentin equivalent to tramadol equivalent present in the oral dosage form ranges from about 0.75;

1 to about 6.5;

1; and

wherein the total weight of the tramadol and substance that comprises gabapentin present in the oral dosage form is less than about 1500 milligrams; and

wherein the controlled delivery dosing structure is adapted to controllably deliver the portion of the substance that comprises tramadol contained by the controlled delivery dosing structure in a delivery dose pattern of from about 0 wt % to about 20 wt % in about 0 to about 4 hrs, about 20 wt % to about 50 wt % in about 0 to about 8 hrs, about 55 wt % to about 85 wt % in about 0 to about 14 hrs, and about 80 wt % to about 100 wt % in about 0 to about 24 hrs, wherein the wt % is based on the total weight of the tramadol present in the controlled delivery dosage form.

13. The oral dosage form of claim 12, wherein the tramadol comprises tramadol HCl.

14. The oral dosage form of claim 12, wherein the substance that comprises gabapentin comprises a complex that comprises gabapentin and an alkyl sulfate salt.

15. The oral dosage form of claim 12, wherein the weight ratio of gabapentin equivalent to tramadol equivalent present in the oral dosage form ranges from about 0.80:

1 to about 5.5;

1.

16. The oral dosage form of claim 12, wherein the oral dosage form comprises an osmotic oral dosage form.

17. An oral controlled delivery dosage form comprising

an oral controlled delivery dosing structure comprising structure that controllably delivers:

(i) a substance that comprises gabapentin, and

(ii) tramadol;

wherein the oral controlled delivery dosing structure is adapted to controllably deliver the substance that comprises gabapentin at a release rate that satisfies the following relationship;

Rate_0-3=(1/F)*Rate_3-10

wherein Rate_0-3 represents a mean release rate for about a three hour period immediately following administration of the dosage form, Rate_3-10 represents a mean release rate for a period from about three hours immediately following administration of the oral dosage form to about ten hours immediately following administration of the oral dosage form, and F=X/Y, wherein X=a colonic bioavailability of gabapentin and Y=upper gastrointestinal tract bioavailability of gabapentin.

18. The oral dosage form of claim 17, wherein the tramadol comprises tramadol HCl.

19. The oral dosage form of claim 17, wherein the substance that comprises gabapentin comprises a complex that comprises gabapentin and an alkyl sulfate salt.

20. A method comprising

(1) providing an oral dosage form comprising:

an oral controlled delivery dosing structure comprising structure that controllably delivers tramadol and a substance that comprises gabapentin; and

wherein the weight ratio of gabapentin equivalent to tramadol equivalent present in the oral dosage form ranges from about 0.75;

1 to about 6.5;

1; and

wherein the total weight of the tramadol and substance that comprises gabapentin present in the oral dosage form is less than about 1500 milligrams; and

wherein the oral controlled delivery dosing structure is adapted to controllably deliver the substance that comprises gabapentin at a rate that is effective to, after a single administration of the oral dosage form to a patient, maintain a gabapentin plasma-drug concentration that is at least about twenty five percent of a gabapentin Cmax throughout a window of at least about fifteen hours duration after a time at which the gabapentin Cmax occurs; and

(2) administering the oral dosage form to a patient.

21. The method of claim 20, wherein the tramadol comprises tramadol HCl.

22. The method of claim 20, wherein the substance that comprises gabapentin comprises a complex that comprises gabapentin and an alkyl sulfate salt.

23. The method of claim 20, wherein the window is of at least about eighteen hours duration after the time at which the gabapentin Cmax occurs

24. The method of claim 20, wherein the weight ratio of gabapentin equivalent to tramadol equivalent present in the oral dosage form ranges from about 0.80:

1 to about 5.5;

1.

25. The method of claim 20, wherein the oral dosage form comprises an osmotic oral dosage form.

26. A method comprising:

(1) providing an oral dosage form comprising;

an oral controlled delivery dosing structure comprising structure that controllably delivers tramadol and a substance that comprises gabapentin;

wherein the weight ratio of gabapentin equivalent to tramadol equivalent present in the oral dosage form ranges from about 0.75;

1 to about 6.5;

1; and

wherein the total weight of the tramadol and substance that comprises gabapentin present in the oral dosage form is less than about 1500 milligrams; and

wherein the controlled delivery dosing structure is adapted to controllably deliver the substance that comprises gabapentin contained by the controlled delivery dosing structure in a delivery dose pattern of from about 0 wt % to about 20 wt % in about 0 to about 4 hrs, about 20 wt % to about 50 wt % in about 0 to about 8 hrs, about 55 wt % to about 85 wt % in about 0 to about 14 hrs, and about 80 wt % to about 100 wt % in about 0 to about 24 hrs, wherein the wt % is based on the total weight of the substance that comprises gabapentin present in the controlled delivery dosage form; and

(2) administering the oral dosage form to a patient.

27. The method of claim 26, wherein the tramadol comprises tramadol HCl.

28. The method of claim 26, wherein the substance that comprises gabapentin comprises a complex that comprises gabapentin and an alkyl sulfate salt.

29. The method of claim 26, wherein the weight ratio of gabapentin equivalent to tramadol equivalent present in the oral dosage form ranges from about 0.80:

1 to about 5.5;

1.

30. The method of claim 26, wherein the oral dosage form comprises an osmotic oral dosage form.

31. A method comprising:

(1) providing an oral dosage form comprising;

an oral controlled delivery dosing structure comprising structure that controllably delivers tramadol and a substance that comprises gabapentin;

wherein the weight ratio of gabapentin equivalent to tramadol equivalent present in the oral dosage form ranges from about 0.75;

1 to about 6.5;

1; and

wherein the total weight of the tramadol and substance that comprises gabapentin present in the oral dosage form is less than about 1500 milligrams; and

wherein the controlled delivery dosing structure is adapted to controllably deliver the portion of the substance that comprises tramadol contained by the controlled delivery dosing structure in a delivery dose pattern of from about 0 wt % to about 20 wt % in about 0 to about 4 hrs, about 20 wt % to about 50 wt % in about 0 to about 8 hrs, about 55 wt % to about 85 wt % in about 0 to about 14 hrs, and about 80 wt % to about 100 wt % in about 0 to about 24 hrs, wherein the wt % is based on the total weight of the tramadol present in the controlled delivery dosage form; and

(2) administering the oral dosage form to a patient.

32. The method of claim 31, wherein the tramadol comprises tramadol HCl.

33. The method of claim 31, wherein the substance that comprises gabapentin comprises a complex that comprises gabapentin and an alkyl sulfate salt.

34. The method of claim 31, wherein the weight ratio of gabapentin equivalent to tramadol equivalent present in the oral dosage form ranges from about 0.80:

1 to about 5.5;

1.

35. The method of claim 31, wherein the oral dosage form comprises an osmotic oral dosage form.

36. A method comprising:

(1) providing an oral controlled delivery dosage form comprising;

an oral controlled delivery dosing structure comprising structure that controllably delivers;

(i) a substance that comprises gabapentin, and

(ii) tramadol;

wherein the oral controlled delivery dosing structure is adapted to controllably deliver the substance that comprises gabapentin at a release rate that satisfies the following relationship;

Rate_0-3=(1/F)*Rate_3-10

wherein Rate_0-3 represents a mean release rate for about a three hour period immediately following administration of the dosage form, Rate_3-10 represents a mean release rate for a period from about three hours immediately following administration of the oral dosage form to about ten hours immediately following administration of the oral dosage form, and F=X/Y, wherein X=a colonic bioavailability of gabapentin and Y=upper gastrointestinal tract bioavailability of gabapentin; and

(2) administering the dosage form to a patient.

37. The method of claim 36, wherein the tramadol comprises tramadol HCl.

38. The method of claim 36, wherein the substance that comprises gabapentin comprises a complex that comprises gabapentin and an alkyl sulfate salt.

39. A pharmaceutical composition comprising

a substance comprising a complex that comprises (i) gabapentin and (ii) a transport moiety;

and

tramadol.

40. The pharmaceutical composition of claim 39, wherein the transport moiety comprises an alkyl sulfate salt.

41. The pharmaceutical composition of claim 40, wherein the alkyl sulfate salt comprises sodium lauryl sulfate.

42. The pharmaceutical composition of claim 39, with the proviso that the substance excludes substances that comprise gabapentin prodrugs wherein the gabapentin prodrug comprises chemical structure that enhances colonic absorption of the gabapentin prodrug as compared to gabapentin.

43. An oral dosage form comprising the pharmaceutical composition of claim 39.

44. The oral dosage form of claim 43, wherein the oral dosage form comprises an oral controlled delivery dosage form.

45. The oral dosage form of claim 44, wherein the oral dosage form comprises an osmotic oral controlled delivery dosage form.

46. The oral dosage form of claim 45, wherein the osmotic oral controlled delivery dosage form comprises a solid osmotic oral controlled delivery dosage form.

47. The oral dosage form of claim 45, wherein the osmotic oral controlled delivery dosage form comprises a liquid osmotic oral controlled delivery dosage form.

48. A method comprising:

(1) providing a pharmaceutical composition comprising a substance comprising a complex that comprises (i) gabapentin and (ii) a transport moiety; and

tramadol; and

(2) administering the pharmaceutical composition to a patient.

49. The method of claim 48, wherein the transport moiety comprises an alkyl sulfate salt.

50. The method of claim 48, wherein the alkyl sulfate salt comprises sodium lauryl sulfate.

51. The method of claim 48, with the proviso that the substance excludes substances that comprise gabapentin prodrugs wherein the gabapentin prodrug comprises chemical structure that enhances colonic absorption of the gabapentin prodrug as compared to gabapentin.