Methods and apparatus for drug delivery involving phase changing formulations

• US 6,528,086 B2
• Filed: 09/28/1999
• Issued: 03/04/2003
• Est. Priority Date: 09/28/1999
• Status: Expired due to Term

• Current Assignee: Crescita Therapeutics Inc.
• Original Assignee: Zars, Inc.
• Inventors: Zhang, Jie
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): GHALI, ISIS A D
• Application Number:
  US09/407,720
• Publication Number:
  US 20020004063A1
• Time in Patent Office: 1,253 Days
• Field of Search: 424/449, 424/443, 424/448
• US Class Current: 424/449
• CPC Class Codes: A61K 9/0034 Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
• CPC Class Codes: A61K 9/7015 Drug-containing film-forming compositions, e.g. spray-on
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 23/02 Local anaesthetics
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Abstract

This invention relates to an apparatus and method of drug delivery on a human body surface. The formulation comprises a drug, a conversion agent capable of converting the formulation from a less solid phase to a coherent, soft, solid phase, and a vehicle medium or carrier for the drug and conversion agent. The drug formulation is applied to this human body surface in its less than solid phase and is subsequently converted to a soft solid phase while the drug is being delivered through the human body surface. After delivery of the drug is complete, the soft solid formulation can be removed or peeled from the body surface as a coherent solid formulation. The drug formulation provides control over drug delivery rates and allows the formulation to be removed without leaving a messy, residual formulation on the body surface.

Claims

1. A method of anesthetizing a human body surface comprising the steps of:

applying a formulation to a human body surface, said formulation comprising;

a local anesthetic;

a conversion agent to facilitate a transformation of said formulation from an initial liquid phase to a peelable coherent, solid phase;

a vehicle medium comprising an evaporable solvent;

converting said formulation to said coherent, solid phase after said formulation is applied to said human body surface by evaporating said evaporable solvent from said formulation; and

controlling the delivery of said local anesthetic into said human body surface by controlling the evaporation time of said evaporable solvent and conversion of said formulation into said peelable coherent, solid phase, wherein said local anesthetic is delivered into said human body surface at a determined and calculated rate sufficient to anesthetize said human body surface during evaporation of said evaporable solvent, said local anesthetic delivery continuing until and is completed upon the substantial evaporation of said evaporable solvent and conversion of said formulation into said coherent solid phase.

2. The method of claim 1, wherein said local anesthetic agent is tetracaine.

3. The method of claim 1, wherein said evaporable solvent is water.

4. The method of claim 1, wherein said human body surface is skin.

5. The method of claim 1, wherein said step of converting said formulation to a coherent, solid phase is accomplished within about 30 minutes, during which complete anesthetization of said human body surface is achieved.

6. The method of claim 1, wherein said step of converting said formulation to a coherent, solid phase is accomplished within about 60 minutes, during which complete anesthetization of said human body surface is achieved.

7. The method of claim 1, further comprising the step of peeling said formulation from said human body surface upon conversion into said coherent, solid phase.

8. The method of claim 1, wherein said conversion agent is polyvinyl alcohol.

9. The method of claim 1, wherein said conversion agent is a thermally reversible gel polymer.

10. The method of claim 9, wherein said thermally reversible gel polymer is Pluronic F127.

11. The method of claim 1, wherein said conversion agent is sodium borate.

12. The method of claim 1, wherein said conversion agent is boric acid.

13. The method of claim 1, wherein said conversion agent is a compound containing salts of boric acid.

14. The method of claim 1, wherein said conversion agent is a compound containing boron.

15. The method of claim 1, wherein said conversion agent is selected from the group of polyvinyl alcohol and carrageenan.

16. The method of claim 1, wherein said conversion agent is selected from the group of:

polyvinyl alcohol, carrageenan, gellan gum, polyvinyl pyrrolidone, sodium carboxymethyl cellulose, hydroxyethyl cellulose, bydroxypropyl cellulose and other cellulose derivatives.

17. The method of claim 1, wherein said conversion agent is a polymer.

18. The method of claim 1, wherein said conversion agent is a compound selected from boric acid and sodium borate.

19. The method of claim 1, wherein said conversion agent is selected from the group of boric acid and salts of boric acid.

20. The method of claim 1, wherein said conversion agent is boron.

21. The method of claim 1, wherein said conversion agent is a compound comprising calcium.

22. The method of claim 1, wherein said conversion agent is a thermal gel capable of becoming more solid at a temperature between 20°

C. to 37°

C.

23. The method of claim 1, wherein said conversion agent is chosen from the group of sodium borate, salts of boric acid and boric acid.

24. The method of claim 1, wherein said transformation is passively triggered.

25. The method of claim 24, wherein said transformation is passively triggered by a change in environment.

26. The method of claim 24, wherein said transformation is passively triggered by a change in the water content of said formulation.

27. The method of claim 24, wherein said transformation is passively triggered by exposing the formulation to human body surface temperature.

28. The method of claim 24, wherein said transformation is passively triggered by exposing the formulation to air.

29. The method of claim 24, wherein said transformation is passively triggered by exposing the formulation to light.

30. The method of claim 24, wherein said transformation is passively triggered by removing the formulation from a storage environment to allow conversion to take place.

31. The method of claim 24, wherein said transformation is passively triggered by exposing the formulation to ambient environmental conditions.

32. The method of claim 31, wherein said ambient environmental conditions are exposure to various wavelengths of electromagnetic radiation, to temperatures, to humidity levels, or to atmospheric gases.

33. The method of claim 1, wherein said transformation is actively triggered.

34. The method of claim 33, wherein said transformation is actively triggered by changing the ambient environment.

35. The method of claim 33, wherein said transformation is actively triggered by changing the chemical makeup of the formulation.

36. The method of claim 33, wherein said transformation is actively triggered by exposing the formulation to a high level of light.

37. The method of claim 33, wherein said transformation is actively triggered by adding a pharmaceutical ingredient to the formulation.

38. The method of claim 33, wherein said transformation is actively triggered by crosslinking a crosslink agent.

39. The method of claim 38, wherein said crosslinking agent comprises covering said formulation with a sheet of material impregnated with said crosslinking agent.

40. The method of claim 33, wherein said transformation is actively triggered by controlling water loss the formulation.

41. The method of claim 33, wherein said transformation is actively triggered by crosslinking a polymer in said formulation using ultraviolet radiation.

42. The method of claim 1, wherein said transformation comprises placing a layer of said formulation onto a human body surface having a temperature of at least 28°

C.

43. The method of claim 1, wherein said transformation is triggered by heating.

44. The method of claim 1, wherein said transformation is triggered by blowing heated air onto said formulation on said human body surface.

45. The method of claim 1, wherein said transformation is triggered by radiating infrared radiation onto said formulation on said human body surface.

46. The method of 1, wherein said transformation is triggered by placing a patch capable of generating heat onto said formulation on said human body surface.

47. The method of 46, the heat of said patch is generated by an exothermic reaction.

48. A method of 1, wherein said transformation significantly reduces the rate of drug delivery.

49. A method of 1, wherein said transformation substantially terminates drug delivery upon completion of said conversion.

50. A method of 1, wherein said transformation prevents over dosing.

51. A method of anesthetizing a human body surface comprising the steps of:

applying a formulation to a human body surface, said formulation comprising;

a local anesthetic;

a conversion agent to facilitate a transformation of said formulation from an initial liquid phase to a peelable coherent, solid phase;

a vehicle medium comprising an evaporable solvent;

converting said formulation to said coherent, solid phase after said formulation is applied to said human body surface by evaporating said evaporable solvent from said formulation; and

delivering of said local anesthetic into said human body surface at sufficient rates that the anesthetizing of said human body surface is achieved during the evaporation of said evaporable solvent;

said evaporable solvent and said formulation having such a property that the complete evaporation of said evaporable solvent from said formulation substantially stops the delivery of said local anesthetic into said human body surface.

52. The method of claim 51, wherein said local anesthetic agent is lidocaine.

53. The method of claim 51, wherein said local anesthetic agent is tetracaine.

54. The method of claim 51, where said evaporable solvent is water.

55. The method of claim 51, wherein said human body surface is skin.

56. The method of claim 51, where said step of converting said formulation to a coherent, solid phase is accomplished within about 30 minutes, during which complete anesthetization of said human body surface is achieved.

57. The method of claim 51, wherein said step of converting said formulation to a coherent, solid phase is accomplished within about 60 minutes, during which complete anesthetization of said human body surface is achieved.

58. The method of claim 51, further comprising the step of peeling said formulation from said human body surface upon conversion into said coherent solid phase.

59. The method of claim 51, wherein said conversion agent is polyvinyl alcohol.

60. The method of claim 51, wherein said conversion agent is a thermally reversible gel polymer.

61. The method of claim 51, wherein said thermally reversible gel polymer is Pluronic F127.

62. The method of claim 51, wherein said conversion agent is selected from the group of polyvinyl alcohol and carrageenan.

63. The method of claim 51, wherein said conversion agent is selected from the group of:

polyvinyl alcohol, carrageenan, gellan gum, polyvinyl pyrrolidone, sodium carboxymethyl cellujose, hydroxyethyl cellulose, hydroxypropyl cellulose and other cellulose derivatives.

64. The method of claim 51, wherein said conversion agent is a polymer.

65. The method of claim 51, wherein said conversion agent is a thermal gel capable of becoming more solid at a temperature between 20°

C. to 37°

C.

66. A method of anesthetizing a human body surface comprising applying a formulation to a human body surface, said formulation comprising:

a local anesthetic;

a conversion agent to facilitate a transformation of said formulation from an initial liquid phase to a peelable coherent, solid phase; and

a vehicle medium comprising an evaporable solvent;

said formulation converting to said coherent, solid phase after said formulation is applied to said human body surface by evaporation of said evaporable solvent from said formulation;

said formulation delivering said local anesthetic into said human body surface during the evaporation of said evaporable solvent and having sufficient delivery rate of said local anesthetic into said human body surface such that the anesthetizing of said human body surface is achieved during the evaporation of said evaporable solvent.

67. The method of claim 66, wherein said conversion agent is polyvinyl alcohol.

68. The method of claim 66, wherein said conversion agent is a polymer.

69. The method of claim 66, wherein said evaporation of said evaporable solvent is facilitated by heat.

70. The method of claim 66, wherein said local anesthetic is tetracaine.

71. The method of claim 66, wherein said local anesthetic is lidocaine.

72. A method of anesthetizing a human body surface comprising the steps of applying a formulation to a human body surface, said formulation comprising:

a local anesthetic;

a conversion agent to facilitate a transformation of said formulation from an initial liquid phase to a peelable coherent, solid phase;

a vehicle medium comprising an evaporable solvent;

converting said formulation to said coherent, solid phase after said formulation is applied to said human body surface by the evaporation of said evaporable solvent from said formulation; and

delivering said local anesthetic into said human body surface at sufficient rates such that the anesthetizing of said human body surface is achieved during the evaporation of said evaporable solvent.

73. The method of claim 72, wherein said converting said formulation to said coherent, solid phase comprises applying said formulation to said human body surface and exposing said formulation to air.

74. The method of claim 72, wherein said delivering of said local anesthetic into said human body surface comprises placing said formulation into contact with said human body surface.

81. The method of claim 72, wherein said conversion agent is polyvinyl alcohol.

75. A method of anesthetizing a human body surface comprising applying a formulation to a human body surface, said formulation comprising:

a local anesthetic;

a conversion agent to facilitate a transformation of said formulation from an initial liquid phase to a peelable coherent, solid phase;

a vehicle medium comprising an evaporable solvent;

said formulation converting to said coherent, solid phase after said formulation is applied to said human body surface by evaporating said evaporable solvent from said formulation; and

said formulation delivering said local anesthetic into said human body surface at sufficient rates that the anesthetizing of said human body surface is achieved during the evaporation of said evaporable solvent and is substantially completed upon the conversion of said formulation into said coherent, solid phase.

82. The method of claim 75, wherein said conversion agent is polyvinyl alcohol.

76. A paste formulation for delivering local anesthetic into a human body surface comprising:

a local anesthetic;

a conversion agent to facilitate the transformation of said formulation from an initial paste phase to a peelable coherent, solid phase; and

an evaporable solvent;

the presence of said solvent being necessary in order for said formulation to deliver said local anesthetic into normal human skin at sufficient rates capable of anesthetizing a normal human within sixty minutes.

77. The formulation of claim 76, wherein the local anesthetic agent is lidocaine.

78. The formulation of claim 76, wherein the local anesthetic agent is tetracaine.

83. The method of claim 76, wherein said conversion agent is polyvinyl alcohol.

79. A method of anesthetizing a human body surface comprising the steps of:

applying a formulation to a human body surface, said formulation comprising;

a local anesthetic;

a conversion agent to facilitate the transformation of said formulation from an initial liquid phase to a peelable coherent, solid phase;

a vehicle medium comprising an evaporable solvent;

converting said formulation to said coherent, solid phase after said formulation is applied to said human body surface by evaporating said evaporable solvent from said formulation; and

delivering said local anesthetic into said human body surfaced at such rates so that the anesthetizing of said human body surface and conversion of said formulation into said solid phase take place within a short time from each other;

said solvent having a property that the complete evaporation of it from the formulation substantially stops the delivering of said local anesthetic into said human body surface.

84. The method of claim 79, wherein said conversion agent is polyvinyl alcohol.

80. A method of anesthetizing a human body surface comprising the steps of:

applying a formulation to a human body surface, said formulation comprising;

a local anesthetic;

a conversion agent to facilitate the transformation of said formulation from an initial liquid phase to a peelable coherent, solid phase;

a vehicle medium comprising and evaporable solvent;

converting said formulation to said coherent, solid phase after said formulation is applied to said human body surface by evaporating said evaporable solvent from said formulation; and

delivery of said local anesthetic into said human body surface by evaporating said evaporable solvent and conversing of said formulation into said peelable coherent, solid phase, wherein said local anesthetic is delivered into said human body surface in the liquid phase sufficient to anesthetize said human body surface during evaporation of said evaporable solvent, said local anesthetic delivery continuing until substantial evaporation of said evaporable solvent.

85. The method of claim 80, wherein said conversion agent is polyvinyl alcohol.