Methods of treatment using a gastric retained gabapentin dosage

• US 7,438,927 B2
• Filed: 10/25/2002
• Issued: 10/21/2008
• Est. Priority Date: 10/25/2001
• Status: Expired due to Term

• Current Assignee: Almatica Pharma LLC (Alvogen Inc.)
• Original Assignee: Depomed Incorporated (Assertio Holdings, Inc.)
• Inventors: Berner, Bret, Hou, Sui Yuen Eddie, Gusler, Gloria M.
• Primary Examiner(s): Sheikh; Humera N
• Application Number:
  US10/280,309
• Publication Number:
  US 20030100611A1
• Time in Patent Office: 2,188 Days
• Field of Search: 424/464, 424/468, 424/474, 424/480
• US Class Current: 424/473
• CPC Class Codes: A61K 31/195 having an amino group
• 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 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0002 Galenical forms characterised by the drug release technique; Application systems commanded by energy
• CPC Class Codes: A61K 9/0065 Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
• 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 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/48 Preparations in capsules, e.g. of gelatin, of chocolate A61K9/0004 takes precedence; bite capsules A61K9/0056
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

A method of treatment for epilepsy and other disease states is described, which comprises the delivery of gabapentin in a gastric retained dosage form.

Claims

1. A method of treating epilepsy in a mammal comprising administering a therapeutically effective amount of a daily dosage of about 200 mg to about 4000 mg of gabapentin or a pharmaceutically acceptable salt thereof, dispersed in a gastric retained dosage form to the mammal in which a fed mode has been induced, wherein the dosage form comprises a single polymer matrix comprising at least one swellable hydrophilic polymer that swells in a dimensionally unrestrained manner by imbibing water to increase its size to promote gastric retention of the dosage form in the stomach of the mammal, and wherein upon contact with water, gabapentin is released by diffusion from the dosage form over a period of at least five hours and at least 40 wt % of the gabapentin is retained in the dosage form one hour after administration.

2. The method of claim 1 wherein the dosage form is administered once-daily.

3. The method of claim 2 wherein the dosage form is administered with a meal.

4. The method of claim 1 wherein the dosage form is administered twice-daily.

5. The method of claim 4 wherein each dosage form is administered with a meal.

6. The method of claim 1 which further comprises administering one or more additional anti-epileptics or anticonvulsants.

7. The method of claim 1 wherein the daily dosage is about 600-2700 mg.

8. The method of claim 1 wherein the daily dosage is about 900-1800 mg.

9. The method of claim 1 wherein the gastric retained dosage form releases gabapentin into the stomach, duodenum and small intestine.

10. The method of claim 1 wherein the dosage form provides administration of at least 80 wt % of the gabapentin to be delivered over a period of about 5-12 hours.

11. The method of claim 1, wherein the hydrophilic polymer is selected from the group consisting of polyethylene oxides, alkyl substituted cellulose materials, and combinations thereof.

12. The method of claim 1 wherein the dosage form further comprises a gas generating agent.

13. The method of claim 12 wherein the gabapentin is contained in a membrane sachet with the gas generating agent.

14. The method of claim 1 wherein the dosage form is a bilayered or multilayered adhesive tablet.

15. The method of claim 1 wherein the gastric retained dosage form is a capsule dosage form form that release gabapentin in the stomach,duodenum and small intestine.

16. The method of claim 1 wherein the gastric retained dosage form is a tablet and the matrix is comprised of poly(ethylene oxide) and hydroxypropylmethylcellulose.

27. The method of claim 1 wherein the hydrophilic polymer is selected from the group consisting of polyethylene oxides, alkyl substituted cellulose materials, and combinations thereof.

28. The method of claim 1 wherein the dosage form further comprises a gas generating agent.

29. The method of claim 28 wherein the gabapentin is contained in a membrane sachet with the gas generating agent.

48. The method of claim 1, wherein the hydrophilic polymer swells to approximately 115% of its original volume within one hour of administration.

51. The method of claim 1, wherein the administering achieves a reduced incidence of side effects to the central nervous system, relative to a non-gastric retained dosage form.

54. The method of claim 1, wherein the hydrophilic polymer has a molecular weight of about 4×

10³ to about 1×

10⁷.

57. The method of claim 16, wherein the poly (ethylene oxide) has a molecular weight of about 2,000,000 daltons to about 7,000,000 daltons.

58. The method of claim 16, wherein the hydroxypropylmethylcellulose has a viscosity of about 4000 cps to about 100,000 cps as measured in a 1% aqueous solution.

60. The method of claim 1, wherein the mammal is a human.

65. The method of claim 1, wherein the dosage form is a bilayered tablet.

17. A method of treating neuropathic pain in a mammal comprising administering a therapeutically effective amount of a daily dosage of about 100 mg to about 4800 mg of gabapentin or a pharmaceutically acceptable salt thereof, dispersed in a gastric retained dosage form to the mammal in which a fed mode has been induced, wherein the dosage form comprises a single polymer matrix comprising at least one swellable hydrophilic polymer that swells in a dimensionally unrestrained manner by imbibing water to increase its size to promote gastric retention of the dosage form in the stomach of the mammal, and wherein upon contact with water, gabapentin is released by diffusion from the dosage form over a period of at least five hours and at least 40 wt% of the gabapentin is retained in the dosage form one hour after administration.

18. The method of claim 17 wherein the dosage form is administered once-daily.

19. The method of claim 18 wherein the dosage form is administered with a meal.

20. The method of claim 17 wherein the dosage form is administered twice-daily.

21. The method of claim 20 wherein each dosage form is administered with a meal.

22. The method of claim 17 further comprising administering one or more therapeutic agents selected from the group consisting of anticonvulsants, tricyclic antidepressants, opioids, and levodopa.

23. The method of claim 17 wherein the daily dosage is about 300-3600 mg.

24. The method of claim 17 wherein the daily dosage is about 900-2400 mg.

25. The method of claim 17 wherein the gastric retained dosage form releases gabapentin to the stomach, duodenum and small intestine.

26. The method of claim 17 wherein the dosage form provides administration of at least 85 wt % of the gabapentin to be delivered over a period of about 5-12 hours.

30. The method of claim 17 wherein the dosage form is a bilayered or multilayered adhesive tablet.

31. The method of claim 17 wherein the dosage form is a capsule dosage form that releases gabapentin in the stomach duodenum and small intestine.

32. The method of claim 17 wherein the gastric retained dosage form is a tablet and the matrix is comprised of poly(ethylene oxide) and hydroxypropylmethylcellulose.

49. The method of claim 17, wherein the hydrophilic polymer swells to approximately 115% of its original volume within one hour of administration.

52. The method of claim 17, wherein the administering achieves a reduced incidence of side effects to the central nervous system, relative to a non-gastric retained dosage form.

55. The method of claim 17, wherein the hydrophilic polymer has a molecular weight of about 4×

10³ to about 1×

10⁷.

61. The method of claim 17, wherein the mammal is a human.

66. The method of claim 17, wherein the dosage form is a bilayered tablet.

33. A method of administering a therapeutically effective amount of a daily dosage of about 100 mg to about 4800 mg of gabapentin to a mammal, comprising administering gabapentin or a pharmaceutically acceptable salt thereof, dispersed in a gastric retained dosage form to the mammal in which a fed mode has been induced and wherein the dosage form comprises a single polymer matrix comprising at least one swellable hydrophilic polymer that swells in a dimensionally unrestrained manner by imbibing water to increase its size to promote gastric retention of the dosage form in the stomach of the mammal, and wherein upon contact with water, gabapentin is released by diffusion from the dosage form over a period of at least five hours and at least 40 wt % of the gabapentin is retained in the dosage form one hour after administration.

34. The method of claim 33 wherein the dosage form is administered once-daily.

35. The method of claim 34 wherein the dosage form is administered with a meal.

36. The method of claim 33 wherein the dosage form is administered twice-daily.

37. The method of claim 36 wherein each dosage form is administered with a meal.

38. The method of claim 33 where the administering is to a mammal diagnosed with or suffering from epilepsy.

39. The method of claim 33 where the administering is to a mammal diagnosed with or suffering from neuropathic pain.

40. The method of claim 33 wherein the gastric retained dosage form releases gabapentin to the stomach, duodenum and small intestine.

41. The method of claim 33 wherein the dosage form provides administration of at least 80 wt % of the gabapentin to be delivered over a period of about 5-12 hours.

42. The method of claim 33 wherein the hydrophilic polymer is selected from the group consisting of polyethylene oxides, alkyl substituted cellulose materials, and combinations thereof.

43. The method of claim 33 wherein the dosage form further comprises a gas generating agent.

44. The method of claim 43 wherein the gabapentin is contained in a membrane sachet with the gas generating agent.

45. The method of claim 33 wherein the dosage form is a bilayered or multilayered adhesive tablet.

46. The method of claim 33 wherein the dosage form is a capsule dosage form that releases gabapentin in the stomach, duodenum and small intestine.

47. The method of claim 33 wherein the gastric retained dosage form is a tablet and the matrix is comprised of poly (ethylene oxide) and hydroxypropylmethylcellulose.

50. The method of claim 33, wherein the hydrophilic polymer swells to approximately 115% of its original volume within one hour of administration.

53. The method of claim 33, wherein the administering achieves a reduced incidence of side effects to the central nervous system, relative to a non-gastric retained dosage form.

56. The method of claim 33, wherein the hydrophilic polymer has a molecular weight of about 4×

10³ to about 1×

10⁷.

59. The method of claim 41, wherein the hydroxypropylmethylcellulose has a viscosity of about 4000 cps to about 100,000 cps as measured in a 1% aqueous solution.

62. The method of claim 33, wherein the mammal is a human.

63. The method of claim 33, wherein the total amount of gabapentin in the daily dosage is about 300-3600 mg.

64. The method of claim 33, wherein the total amount of gabapentin in the daily dosage is about 900-2400 mg.

67. The method of claim 33, wherein the dosage form is a bilayered tablet.