Oral osmotic device for delivering nicotine

• US 5,147,654 A
• Filed: 11/15/1991
• Issued: 09/15/1992
• Est. Priority Date: 07/23/1990
• Status: Expired due to Fees

• Current Assignee: ALZA Corporation (Johnson & Johnson)
• Original Assignee: ALZA Corporation (Johnson & Johnson)
• Inventors: Place, Virgil A., Wong, Patrick S. L., Barclay, Brian L., Childers, Jerry D.
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): BROUILLETTE, D GABRIELLE
• Application Number:
  US07/793,058
• Time in Patent Office: 305 Days
• Field of Search: 424/473, 424/435, 424/478
• US Class Current: 424/473
• CPC Class Codes: A61K 31/465 Nicotine; Derivatives thereof
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas

Abstract

An osmotic device (10) for the controlled systemic delivery of nicotine through an oral mucosal membrane of a human patient is disclosed. The device (10) has a size and shape adapting it to be comfortably retained in the mouth for extended periods of time. The device (10) comprises a semipermeable wall (12) surrounding a compartment (13) containing a nicotine salt (14) and optionally an alkaline salt which is capable of reacting with the nicotine salt in the presence of water to form nicotine base. The conversion of nicotine salt to nicotine base may take place within the device (10) and/or outside the device and in the patient'"'"'s mouth. Nicotine base and/or salt is delivered from the compartment (13) through a passageway (17) in the wall (12). The nicotine salt exhibits good stability and shelf life while the nicotine base exhibits excellent absorption through oral mucosal membranes.

Claims

1. An osmotic device for the controlled systemic delivery of nicotine base through an oral mucosal membrane in an oral cavity over an extended delivery period, including:

a semipermeable wall surrounding and forming a compartment containing a nicotine salt which is capable of reacting with an aqueous fluid to form nicotine base, the wall being formed of a material which is permeable to the passage of an aqueous fluid present in the oral cavity, and a passageway through the semipermeable wall for delivering the nicotine base formed in the compartment to the oral mucosal membrane, wherein the device when in operation in the oral cavity imbibes the aqueous fluid through the wall into the compartment, thereby initiating a chemical reaction between the nicotine salt and the aqueous fluid to produce nicotine base which is delivered from the compartment through the passageway and into the oral cavity over time.

2. The osmotic device of claim 1, wherein the nicotine salt is selected from the group consisting of nicotine hydrochloride, nicotine dihydrochloride, nicotine sulfate, nicotine monotartrate, nicotine bitartrate, nicotine salicylate and nicotine zinc chloride monohydrate.

3. The osmotic device of claim 1, wherein the nicotine salt is selected from the group consisting of nicotine monotartrate and nicotine bitartrate.

4. The osmotic device of claim 1, wherein the compartment also contains an alkaline salt which is capable of reacting with the nicotine salt in the presence of the aqueous fluid to form nicotine base.

5. The osmotic device of claim 4, wherein the alkaline salt is osmotically active.

6. The osmotic device of claim 4, wherein the alkaline salt has a pH of greater than about 7.

7. The osmotic device of claim 4, wherein the alkaline salt is selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trisodium phosphate, disodium hydrogen phosphate, sodium oxylate, sodium succinate, sodium citrate, and sodium salicylate.

8. The osmotic device of claim 4, wherein the alkaline salt comprises sodium bicarbonate.

9. The osmotic device of claim 1, wherein the device has a size and shape suitable for comfortably retaining the device in the oral cavity for the extended delivery period.

10. The osmotic device of claim 1, wherein the device has a smooth oval shape with an aspect ratio in the range of about 1.2:

1 to about 3;

1, a height of about 0.5 to about 10 mm, and a volume of less than about 2 cm³.

11. The osmotic device of claim 1, wherein the compartment further contains a gelling agent which substantially prevents the wall from collapsing under conditions of use in the oral cavity.

12. The osmotic device of claim 11, wherein the gelling agent is selected from the group consisting of acacia, agar-agar, calcium carrageenan, alginic acid, algin, agarose powder, collagen, colloidal magnesium silicate, colloidal silicon dioxide, cross-linked polyacrylic acid, polyvinyl pyrrolidone, sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyethylene oxide, pectin, gelatin and calcium silicate.

13. The osmotic device of claim 11, wherein the gelling agent is selected from the group consisting of polyethylene oxide and hydroxypropylmethylcellulose.

14. The osmotic device of claim 1, wherein compartment contains a layer of a hydrophilic polymer.

15. The osmotic device of claim 14, wherein the hydrophilic polymer is a cross-linked hydrogel.

16. The osmotic device of claim 1, wherein the extended delivery period is about 0.5 to 12 hours.

17. The osmotic device of claim 1, wherein the extended delivery period is about 1 to 6 hours.

18. A method of systemically delivering nicotine base through an oral mucosal membrane in an oral cavity over an extended delivery period comprising:

placing into the oral cavity an osmotic device including a semipermeable wall surrounding and forming a compartment containing a nicotine salt which is capable of reacting with an aqueous fluid present in the oral cavity to form nicotine base, the wall being permeable to the aqueous fluid, the device having a passageway through the semipermeable wall;

delivering the nicotine base formed in the compartment to the oral mucosal membrane at a controlled rate over the extended delivery period by imbibing the aqueous fluid through the wall into the compartment, thereby initiating a chemical reaction between the nicotine salt and the aqueous fluid to produce nicotine base and delivering the nicotine base from the compartment through the passageway over the extended delivery period.

19. The method of claim 18, wherein the nicotine salt is selected from the group consisting of nicotine hydrochloride, nicotine dihydrochloride, nicotine sulfate, nicotine monotartrate, nicotine bitartrate, nicotine salicylate and nicotine zinc chloride monohydrate.

20. The method of claim 18, wherein the nicotine salt is selected from the group consisting of nicotine monotartrate and nicotine bitartrate.

21. The method of claim 18, wherein the compartment also contains an alkaline salt which is capable of reacting with the nicotine salt in the presence of the aqueous fluid to form nicotine base.

22. The method of claim 21, wherein the alkaline salt is osmotically active.

23. The method of claim 21, wherein the alkaline salt has a pH of greater than about 7.

24. The method of claim 21, wherein the alkaline salt is selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trisodium phosphate, disodium hydrogen phosphate, sodium oxylate, sodium succinate, sodium citrate and sodium salicylate.

25. The method of claim 21, wherein the alkaline salt comprises sodium bicarbonate.

26. The method of claim 18, wherein the device has a smooth oval shape with an aspect ratio in the range of about 1.2:

1 to about 3;

1, a height of about 0.5 to about 10 mm, and a volume of less than about 2 cm³.

27. The method of claim 18, wherein the extended delivery period is about 0.5 to 12 hours.

28. The method of claim 18, wherein the compartment further contains a gelling agent which substantially prevents the wall from collapsing under conditions of use in the oral cavity.

29. The method of claim 28, wherein the gelling agent is selected from the group consisting of acacia, agar-agar, calcium carrageenan, alginic acid, algin, agarose powder, collagen, colloidal magnesium silicate, colloidal silicon dioxide, cross-linked polyacrylic acid, polyvinyl pyrrolidone, sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyethylene oxide, pectin, gelatin and calcium silicate.

30. The method of claim 28, wherein the gelling agent is selected from the group consisting of polyethylene oxide and hydroxypropylmethylcellulose.

31. The method of claim 18, wherein the compartment contains a layer of a hydrophilic polymer.

32. The method of claim 31, wherein the hydrophilic polymer is a cross-linked hydrogel.

33. The method of claim 18, wherein the extended delivery period is about 0.5 to 12 hours.

34. The method of claim 18, wherein the extended delivery period is about 1 to 6 hours.

35. An osmotic device for the controlled systemic delivery of nicotine base through an oral mucosal membrane in an oral cavity over an extended delivery period including:

a semipermeable wall surrounding and forming a compartment containing a nicotine salt which is capable or reacting with an aqueous fluid to form nicotine base, the wall being formed of a material which is permeable to the passage of an aqueous fluid present in the oral cavity, and a passageway through the semipermeable wall for delivering nicotine to the oral mucosal membrane, wherein the device when in operation in the oral cavity imbibes the aqueous fluid through the wall into the compartment, thereby converting the nicotine salt to nicotine base which is delivered through the oral mucosal membrane over time.

36. The osmotic device of claim 35, wherein the nicotine salt is selected from the group consisting of nicotine hydrochloride, nicotine dihydrochloride, nicotine sulfate, nicotine monotartrate, nicotine bitartrate, nicotine salicylate and nicotine zinc chloride monohydrate.

37. The osmotic device of claim 35, wherein the nicotine salt is selected from the group consisting of nicotine monotartrate and nicotine bitartrate.

38. The osmotic device of claim 35, wherein the compartment also contains an alkaline salt which is capable of enhancing the conversion of the nicotine salt to nicotine base.

39. The osmotic device of claim 38, wherein the alkaline salt is osmotically active.

40. The osmotic device of claim 38, wherein the alkaline salt has a pH of greater than about 7.

41. The osmotic device of claim 38, wherein the alkaline salt is selected fro mthe group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trisodium phosphate, disodium hydrogen phosphate, sodium oxylate, sodium succinate, sodium citrate, and sodium salicylate.

42. The osmotic device of claim 38, wherein the alkaline salt comprises sodium bicarbonate.

43. The osmotic device of claim 35, wherein the device has a size and shape suitable for comfortably retaining the device in the oral cavity for the extended delivery period.

44. The osmotic device of claim 35, wherein the device has a smooth oval shape with an aspect ratio in the range of about 1.2:

1 to about 3;

1, a height of about 0.5 mm to about 10 mm, and a volume of less than about 2 cm³.

45. The osmotic device of claim 35, wherein the compartment further contains a suspending or gelling agent which substantially prevents the wall from collapsing under conditions of use in the oral cavity.

46. The osmotic device of claim 45, wherein the suspending or gelling agent is selected from the group consisting of acacia, agar-agar, calcium carrageenan, alginic acid, algin, alginates, agarose powder, collagen, colloidal magnesium silicate, colloidal silicon dioxide, cross-linked polyacrylic acid, polyvinyl pyrrolidone, sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyethylene oxide, pectin, gelatin and calcium silicate.

47. The osmotic device of claim 45, wherein the suspending or gelling agent comprises hydroxypropylcellulose.

48. The osmotic device of claim 35, wherein the compartment contains a layer of a hydrophilic polymer.

49. The osmotic device of claim 48, wherein the hydrophilic polymer is a cross-linked hydrogel.

50. The osmotic device of claim 48, wherein the hydrophilic polymer is a polysaccharide.

51. The osmotic device of claim 35, wherein the extended delivery period is about 0.5 to 12 hours.

52. The osmotic device of claim 35, wherein the extended delivery period is about 1 to 6 hours.

53. The osmotic device of claim 35, wherein at least a portion of the nicotine salt is converted to nicotine base within the compartment and delivered through the passageway and into the oral cavity.

54. The osmotic device of claim 35, wherein at least a portion of the nicotine salt is converted to nicotine base outside the device and within the oral cavity.

55. A method of systemically delivering nicotine base through an oral mucosal membrane in an oral cavity over an extended delivery period comprising:

placing into the oral cavity an osmotic device including a semipermeable wall surrounding and forming a compartment containing a nicotine salt which is capable of reacting with an aqueous fluid present in the oral cavity to form nicotine base, the wall being permeable to the aqueous fluid, the device having a passageway through the semipermeable wall;

delivering the formed nicotine base to the oral mucosal membrane at a controlled rate over the extended delivery period by imbibing the aqueous fluid through the wall into the compartment, thereby converting the nicotine salt to nicotine base which is delivered through the oral mucosal membrane over the extended delivery period.

56. The method of claim 55, wherein the nicotine salt is selected from the group consisting of nicotine hydrochloride, nicotine dihydrochloride, nicotine sulfate, nicotine monotartrate, nicotine bitartrate, nicotine salicylate and nicotine zinc chloride monohydrate.

57. The method of claim 55, wherein the nicotine salt is selected from the group consisting of nicotine monotartrate and nicotine bitartrate.

58. The method of claim 55, wherein the nicotine salt is selected from the group consisting of nicotine monotartrate and nicotine bitartrate.

59. The method of claim 58, wherein the alkaline salt is osmotically active.

60. The method of claim 58, wherein the alkaline salt has a pH of greater than about 7.

61. The method of claim 58, wherein the alkaline salt is selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trisodium phosphate, disodium hydrogen phosphate, sodium oxylate, sodium succinate, sodium citrate and sodium salicylate.

62. The method of claim 58, wherein the alkaline salt comprises sodium bicarbonate.

63. The method of claim 55, wherein the device has a smooth oval shape with an aspect ratio in the range of about 1.2:

1 to about 3;

1, a height of about 0.5 mm to about 10 mm, and a volume of less than about 2 cm³.

64. The method of claim 55, wherein the extended delivery period is about 0.5 to 12 hours.

65. The method of claim 55, wherein the compartment further contains a suspending or a gelling agent which substantially prevents the wall from collapsing under conditions of use in the oral cavity.

66. The method of claim 65, wherein the suspending or gelling agent is selected from the group consisting of acacia, agar-agar, calcium carrageenan, alginic acid, algin, alginates, agarose powder, collagen, colloidal magnesium silicate, colloidal silicon dioxide, cross-linked polyacrylic acid, polyvinyl pyrrolidone, sodium carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, polyethylene oxide, pectin, gelatin and calcium silicate.

67. The method of claim 65, wherein the suspending or gelling agent comprises hydroxypropylcellulose.

68. The method of claim 55, wherein the compartment contains a layer of a hydrophilic polymer.

69. The method of claim 68, wherein the hydrophilic polymer is a cross-linked hydrogel.

70. The method of claim 68, wherein the hydrophilic polymer is a polysaccharide.

71. The method of claim 55, wherein the extended delivery period is about 0.5 to 12 hours.

72. The method of claim 55, wherein the extended delivery period is about 1 to 6 hours.

73. The method of claim 55, wherein at least a portion of the nicotine salt is converted to nicotine base within the compartment and delivered through the passageway and into the oral cavity.

74. The method of claim 55, wherein at least a portion of the nicotine salt is converted to nicotine base outside the device and within the oral cavity.