Active drug delivery in the gastrointestinal tract

• US 20050058701A1
• Filed: 07/29/2004
• Published: 03/17/2005
• Est. Priority Date: 01/29/2003
• Status: Abandoned Application

• Current Assignee: E-Pill Pharma, Ltd.
• Original Assignee: E-Pill Pharma, Ltd.
• Inventors: Gross, Yossi, Sela, Yoram, Belsky, Ziv, Goldstein, Daniel, Lev, Rina
• Application Number:
  US10/901,742
• Publication Number:
  US 20050058701A1
• Time in Patent Office: Days
• US Class Current: 424/451
• CPC Class Codes: A61B 1/00016 using wireless means
• CPC Class Codes: A61B 1/00156 using self propulsion
• CPC Class Codes: A61B 1/041 Capsule endoscopes for imaging
• CPC Class Codes: A61B 17/3203 Fluid jet cutting instruments
• CPC Class Codes: A61B 18/02 by cooling, e.g. cryogenic techniques devices for cooling specific reflex points of the body within cell-life limits A61H39/06
• CPC Class Codes: A61B 18/14 Probes or electrodes therefor
• CPC Class Codes: A61B 18/20 using laser
• CPC Class Codes: A61B 34/70 Manipulators specially adapted for use in surgery
• CPC Class Codes: A61B 34/72 Micromanipulators
• CPC Class Codes: A61B 5/0008 Temperature signals
• CPC Class Codes: A61B 5/01 Measuring temperature of body parts ; Diagnostic temperature sensing, e.g. for malignant or inflamed tissue clinical contact thermometers G01K13/20
• CPC Class Codes: A61B 5/036 by means introduced into body tracts A61B5/032 and A61B5/035 take precedence
• CPC Class Codes: A61B 5/073 Intestinal transmitters
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14539 for measuring pH
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/4839 combined with drug delivery
• CPC Class Codes: A61J 3/07 into the form of capsules or similar small containers for oral use
• CPC Class Codes: A61K 9/0004 Osmotic delivery systems; Sustained release driven by osmosis, thermal energy or gas
• CPC Class Codes: A61K 9/0009 involving or responsive to electricity, magnetism or acoustic waves; Galenical aspects of sonophoresis, iontophoresis, electroporation or electroosmosis microelectromechanical systems A61K9/0097
• CPC Class Codes: A61K 9/0097 : Micromachined devices; Microelectromechanical systems [MEMS]; Devices obtained by lithographic treatment of silicon; Devices comprising chips intradermal microneedle arrays A61K9/0021; MEMS in general B81B7/02
• CPC Class Codes: A61K 9/4808 : characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61M 31/002 : Devices for releasing a drug at a continuous and controlled rate for a prolonged period of time artificial gland structures or devices A61F2/022; intra-uterine contraceptive devices A61F6/14; tampons for introducing into the vagina A61F13/20, A61L15/00; suppositories or bougies for intra-vaginal or intra-uterine application A61K9/02; physical forms of medicinal preparations for sustained or differential drug release A61K9/20, A61K9/50
• CPC Class Codes: A61N 1/05 : for implantation or insertion into the body, e.g. heart electrode A61N1/06 takes precedence
• CPC Class Codes: A61N 1/306 : Arrangements where at least part of the apparatus is introduced into the body
• CPC Class Codes: A61N 1/325 : for iontophoresis, i.e. transfer of media in ionic state by an electromotoric force into the body electrodes for external use A61N1/0428
• CPC Class Codes: A61N 1/327 : for enhancing the absorption properties of tissue, e.g. by electroporation
• CPC Class Codes: A61N 1/36007 : of urogenital or gastrointestinal organs, e.g. for incontinence control
• CPC Class Codes: A61N 1/3605 : Implantable neurostimulators for stimulating central or peripheral nerve system
• CPC Class Codes: A61N 1/37205 : Microstimulators, e.g. implantable through a cannula
• CPC Class Codes: A61N 1/3756 : Casings with electrodes thereon, e.g. leadless stimulators
• CPC Class Codes: G01K 13/20 : Clinical contact thermometers for use with humans or animals

Abstract

Apparatus for drug administration is provided, including an ingestible capsule, which includes a drug, stored by the capsule, and an environmentally-sensitive mechanism, adapted to change a state thereof responsively to a disposition of the capsule within a gastrointestinal (GI) tract of a subject. The capsule further includes first and second electrodes, and a control component, adapted to facilitate passage of the drug, in response to a change of state of the environmentally-sensitive mechanism, through an epithelial layer of the GI tract by driving the first and second electrodes to apply a series of pulses at a current of less than about 5 mA, at a frequency of between about 12 Hz and about 24 Hz, and with a pulse duration of between about 0.5 milliseconds and about 3 milliseconds.

Claims

1. Apparatus for drug administration, comprising an ingestible capsule, which comprises:

a drug, stored by the capsule;

an environmentally-sensitive mechanism, adapted to change a state thereof responsively to a disposition of the capsule within a gastrointestinal (GI) tract of a subject;

first and second electrodes; and

a control component, adapted to facilitate passage of the drug, in response to a change of state of the environmentally-sensitive mechanism, through an epithelial layer of the GI tract by driving the first and second electrodes to apply a series of pulses at a current of less than about 5 mA, at a frequency of between about 12 Hz and about 24 Hz, and with a pulse duration of between about 0.5 milliseconds and about 3 milliseconds.

2. The apparatus according to claim 1, wherein the pulses include monophasic rectangular pulses, and wherein the control component is adapted to drive the first and second electrodes to apply the series of monophasic rectangular pulses.

3. The apparatus according to claim 1, wherein the first and second electrodes comprise stainless steel.

4. The apparatus according to claim 1,

wherein the environmentally-sensitive mechanism comprises a sensor adapted to sense an indication of a distance traveled by the capsule in the GI tract, and

wherein the environmentally-sensitive mechanism is adapted to undergo the change of state responsive to the distance.

5. The apparatus according to claim 1, wherein the environmentally-sensitive mechanism comprises a camera, adapted to image the GI tract, and wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses in response to an image acquired by the camera.

6. The apparatus according to claim 1, wherein the disposition of the capsule includes a temperature in a vicinity of the capsule, wherein the environmentally-sensitive mechanism comprises a temperature sensor, and wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses in response to the temperature sensed by the temperature sensor.

7. The apparatus according to claim 1, wherein the disposition of the capsule includes a pH in a vicinity of the capsule, wherein the environmentally-sensitive mechanism comprises a pH sensor, and wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses in response to the pH sensed by the pH sensor.

8. The apparatus according to claim 1, wherein the environmentally-sensitive mechanism comprises a sensor, adapted to sense a characteristic of the GI tract, and wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses in response to the sensed characteristic.

9. The apparatus according to claim 1, wherein the control component is adapted to:

drive the first and second electrodes to apply the series of pulses, and

drive an iontophoretic current between the first and second electrodes.

10. The apparatus according to claim 1, wherein the control component is adapted to configure the series of pulses using parameters selected at least in part responsively to the disposition of the capsule within the GI tract.

11. The apparatus according to claim 1, wherein the control component is adapted to configure the series of pulses using parameters selected at least in part responsively to a property of the drug.

12. The apparatus according to claim 1, wherein the capsule comprises a central portion, intermediate the first and second electrodes, a shape of the central portion being such as to reduce current flow within a lumen of the GI tract.

13. The apparatus according to claim 1, wherein the capsule comprises a central portion, intermediate the first and second electrodes, the central portion having a diameter that is such as to bring the central portion in contact with the epithelial layer of the GI tract, whereby to reduce current flow within a lumen of the GI tract.

14. The apparatus according to claim 1, wherein the capsule comprises a self-expansible central portion, intermediate the first and second electrodes, the central portion adapted to expand, in response to being in the GI tract, to have a diameter that is such as to bring the central portion in contact with the epithelial layer of the GI tract, whereby to reduce current flow within a lumen of the GI tract.

15. The apparatus according to claim 1, wherein the capsule comprises a central portion, intermediate the first and second electrodes, an outer surface of the central portion comprising a hydrophobic material.

16. The apparatus according to claim 1, wherein the capsule comprises a central portion, intermediate the first and second electrodes, an outer surface of the central portion comprising a lipophilic material.

17. The apparatus according to claim 1, wherein the environmentally-sensitive mechanism is essentially entirely biodegradable.

18. The apparatus according to claim 1, wherein the first and second electrodes and the control component are essentially entirely biodegradable.

19. The apparatus according to claim 1, wherein at least 80% of the mass of the capsule is biodegradable.

20. The apparatus according to claim 19, wherein at least 95% of the mass of the capsule is biodegradable.

21. The apparatus according to-claim 20, wherein essentially the entire capsule is biodegradable.

22. The apparatus according to claim 1, wherein the environmentally-sensitive mechanism comprises a coating on a surface of the capsule.

23. The apparatus according to claim 22, wherein the coating comprises a pH-sensitive coating.

24. The apparatus according to claim 1, wherein the control component is adapted to apply the series of pulses at a current of between about 2 mA and about 4 mA.

25. The apparatus according to claim 24, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a current of about 3 mA.

26. The apparatus according to claim 1, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a frequency of between about 16 Hz and about 20 Hz.

27. The apparatus according to claim 26, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a frequency of about 18 Hz.

28. The apparatus according to claim 1, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses with a pulse duration of between about 0.5 milliseconds and about 1.5 milliseconds.

29. The apparatus according to claim 28, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses with a pulse duration of about 1 millisecond.

30. The apparatus according to claim 1, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses for a period of between about 1 and about 360 minutes.

31. The apparatus according to claim 30, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses for a period of between about 60 and about 240 minutes.

32. Apparatus for administration of a drug, comprising an ingestible capsule adapted to store the drug, the capsule comprising:

an environmentally-sensitive mechanism, adapted to change a state thereof responsively to a disposition of the capsule within a gastrointestinal (GI) tract of a subject;

first and second electrodes; and

a control component, adapted to facilitate passage of the drug, in response to a change of state of the environmentally-sensitive mechanism, through an epithelial layer of the GI tract by driving the first and second electrodes to apply a series of pulses at a current of less than about 5 mA, at a frequency of between about 12 Hz and about 24 Hz, and with a pulse duration of between about 0.5 milliseconds and about 3 milliseconds.

33. The apparatus according to claim 32, wherein the control component is adapted to apply the series of pulses at a current of between about 2 mA and about 4 mA.

34. The apparatus according to claim 33, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a current of about 3 mA.

35. The apparatus according to claim 32, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a frequency of between about 16 Hz and about 20 Hz.

36. The apparatus according to claim 35, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a frequency of about 18 Hz.

37. The apparatus according to claim 32, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses with a pulse duration of between about 0.5 milliseconds and about 1.5 milliseconds.

38. The apparatus according to claim 37, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses with a pulse duration of about 1 millisecond.

39. The apparatus according to claim 32, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses for a period of between about 1 and about 360 minutes.

40. The apparatus according to claim 39, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses for a period of between about 60 and about 240 minutes.

41. Apparatus for facilitating administration of a drug contained in a pill, the apparatus comprising an ingestible housing, which is not adapted to contain the drug or to be assembled in an integral unit with the drug, the housing comprising:

an ingestible environmentally-sensitive mechanism, adapted to change a state thereof responsive to a disposition thereof within a gastrointestinal (GI) tract of a subject;

first and second electrodes; and

a control component, adapted to facilitate passage of the drug, in response to a change of state of the environmentally-sensitive mechanism, through an epithelial layer of the GI tract by driving the first and second electrodes to apply a series of pulses at a current of less than about 5 mA, at a frequency of between about 12 Hz and about 24 Hz, and with a pulse duration of between about 0.5 milliseconds and about 3 milliseconds.

42. The apparatus according to claim 41,

wherein the environmentally-sensitive mechanism comprises a sensor adapted to sense an indication of a distance traveled by the housing in the GI tract, and

wherein the environmentally-sensitive mechanism is adapted to undergo the change of state responsive to the distance.

43. The apparatus according to claim 41, wherein the environmentally-sensitive mechanism comprises a camera, adapted to image the GI tract, and wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses in response to an image acquired by the camera.

44. The apparatus according to claim 41, wherein the disposition of the environmentally-sensitive mechanism includes a temperature in a vicinity of the environmentally-sensitive mechanism, wherein the environmentally-sensitive mechanism comprises a temperature sensor, and wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses in response to the temperature sensed by the temperature sensor.

45. The apparatus according to claim 41, wherein the disposition of the environmentally-sensitive mechanism includes a pH in a vicinity of the environmentally-sensitive mechanism, wherein the environmentally-sensitive mechanism comprises a pH sensor, and wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses in response to the pH sensed by the pH sensor.

46. The apparatus according to claim 41, wherein the environmentally-sensitive mechanism comprises a sensor, adapted to sense a characteristic of the GI tract, and wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses in response to the sensed characteristic.

47. The apparatus according to claim 41, wherein the environmentally-sensitive mechanism is adapted to undergo the change of state generally at an expected time of release of the drug from the drug pill.

48. The apparatus according to claim 41, wherein the environmentally-sensitive mechanism comprises a coating on a surface of the housing.

49. The apparatus according to claim 48, wherein the coating comprises a pH-sensitive coating.

50. The apparatus according to claim 41, wherein the control component is adapted to apply the series of pulses at a current of between about 2 mA and about 4 mA.

51. The apparatus according to claim 50, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a current of about 3 mA.

52. The apparatus according to claim 41, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a frequency of between about 16 Hz and about 20 Hz.

53. The apparatus according to claim 52, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a frequency of about 18 Hz.

54. The apparatus according to claim 41, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses with a pulse duration of between about 0.5 milliseconds and about 1.5 milliseconds.

55. The apparatus according to claim 54, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses with a pulse duration of about 1 millisecond.

56. The apparatus according to claim 41, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses for a period of between about 1 and about 360 minutes.

57. The apparatus according to claim 56, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses for a period of between about 60 and about 240 minutes.

58. Apparatus for use with a drug pill, the apparatus comprising:

a coupling mechanism, adapted to couple the drug pill to the apparatus;

first and second electrodes; and

a control component, adapted to facilitate passage of a drug contained in the drug pill through an epithelial layer of a gastrointestinal (GI) tract of a subject by driving the first and second electrodes to apply a series of pulses at a current of less than about 5 mA, at a frequency of between about 12 Hz and about 24 Hz, and with a pulse duration of between about 0.5 milliseconds and about 3 milliseconds.

59. The apparatus according to claim 58, wherein the drug pill includes a commercially-available drug pill, and wherein the coupling mechanism is adapted to couple the commercially-available drug pill to the apparatus.

60. The apparatus according to claim 58, wherein the coupling mechanism comprises an adhesive.

61. The apparatus according to claim 58, wherein the coupling mechanism comprises at least one of the electrodes.

62. The apparatus according to claim 61, wherein the at least one of the electrodes is configured to surround a portion of the drug pill once the drug pill has been coupled to the apparatus.

63. The apparatus according to claim 58, wherein the control component is adapted to apply the series of pulses at a current of between about 2 mA and about 4 mA.

64. The apparatus according to claim 63, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a current of about 3 mA.

65. The apparatus according to claim 58, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a frequency of between about 16 Hz and about 20 Hz.

66. The apparatus according to claim 65, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a frequency of about 18 Hz.

67. The apparatus according to claim 58, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses with a pulse duration of between about 0.5 milliseconds and about 1.5 milliseconds.

68. The apparatus according to claim 67, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses with a pulse duration of about 1 millisecond.

69. The apparatus according to claim 58, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses for a period of between about 1 and about 360 minutes.

70. The apparatus according to claim 69, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses for a period of between about 60 and about 240 minutes.

71. Apparatus for facilitating administration of a drug to a subject, the apparatus comprising:

a sensor unit, which comprises;

a sensor, adapted to detect an indication of a concentration of a substance in a blood circulation of the subject; and

a wireless transmitter, adapted to wirelessly transmit the indication; and

an ingestible capsule, which comprises;

a wireless receiver, adapted to receive the indication;

first and second electrodes; and

a control component, adapted to facilitate passage of the drug through an epithelial layer of a gastrointestinal (GI) tract of the subject by driving the first and second electrodes to apply a series of pulses at a current of less than about 5 mA, at a frequency of between about 12 Hz and about 24 Hz, and with a pulse duration of between about 0.5 milliseconds and about 3 milliseconds.

72. The apparatus according to claim 71, wherein the substance includes the drug, and wherein the sensor is adapted to detect the indication of the concentration of the drug in the blood circulation.

73. The apparatus according to claim 71,

wherein the substance includes a calibrating substance,

wherein the sensor is adapted to detect the indication of the concentration of the calibrating substance in the blood circulation, and

wherein the control component is adapted to facilitate the passage of the calibrating substance and the drug through the epithelial layer of the GI tract, responsively to the received indication.

74. The apparatus according to claim 71, wherein the sensor comprises a noninvasive external sensor.

75. The apparatus according to claim 71, wherein the sensor comprises an invasive sensor.

76. The apparatus according to claim 71, wherein the ingestible capsule is adapted to store the drug.

77. The apparatus according to claim 71, wherein the ingestible capsule is not adapted to contain the drug or to be assembled in an integral unit with the drug.

78. The apparatus according to claim 71, wherein the drug is contained in a drug pill, and wherein the ingestible capsule comprises a coupling mechanism, adapted to couple the drug pill to the ingestible capsule.

79. The apparatus according to claim 71,

wherein the ingestible capsule comprises an environmentally-sensitive mechanism, adapted to change a state thereof responsively to a disposition of the capsule within the GI tract, and

wherein the control component is adapted to facilitate the passage of the drug through the epithelial layer in response to a change of state of the environmentally-sensitive mechanism.

80. The apparatus according to claim 71,

wherein the indication includes respective first and second indications, sensed at respective first and second times,

wherein the wireless transmitter is adapted to transmit the first indication subsequent to the first time, and to transmit the second indication subsequent to the second time, and

wherein the control component is adapted to drive the first and second electrodes to apply first and second series of pulses, responsive to the first and second indications.

81. The apparatus according to claim 80, wherein the sensor unit is adapted to space the first and second times by at least 10 minutes.

82. The apparatus according to claim 80, wherein the control component is adapted to regulate a parameter of at least one of the series of pulses, responsive to at least one of the indications.

83. The apparatus according to claim 71,

wherein the ingestible capsule comprises a capsule wireless transmitter,

wherein the sensor unit comprises a sensor unit wireless receiver, and

wherein the ingestible capsule is adapted to wirelessly notify the sensor unit of a property of the capsule, via the capsule wireless transmitter and the sensor unit wireless receiver.

84. The apparatus according to claim 83, wherein the property is selected from the list consisting of:

a location of the capsule, a status of the control component, a pH level of the GI tract, and a temperature of the GI tract, and wherein the capsule is adapted to wirelessly notify the sensor of the selected property.

85. The apparatus according to claim 71, wherein the substance includes a chemical, the blood concentration of which is affected by a blood concentration of the drug, and wherein the sensor is adapted to detect the indication of the concentration of the chemical in the blood circulation.

86. The apparatus according to claim 85, wherein the chemical is selected from the list consisting of:

glucose, growth hormone, and hemoglobin-bound oxygen, and wherein the sensor is adapted to detect the indication of the concentration of the selected chemical in the blood circulation.

87. The apparatus according to claim 71, wherein the control component is adapted to apply the series of pulses at a current of between about 2 mA and about 4 mA.

88. The apparatus according to claim 87, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a current of about 3 mA.

89. The apparatus according to claim 71, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a frequency of between about 16 Hz and about 20 Hz.

90. The apparatus according to claim 89, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a frequency of about 18 Hz.

91. The apparatus according to claim 71, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses with a pulse duration of between about 0.5 milliseconds and about 1.5 milliseconds.

92. The apparatus according to claim 91, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses with a pulse duration of about 1 millisecond.

93. The apparatus according to claim 71, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses for a period of between about 1 and about 360 minutes.

94. The apparatus according to claim 93, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses for a period of between about 60 and about 240 minutes.

95. Apparatus for facilitating administration of a drug to a subject, the apparatus comprising:

a sensor unit, which comprises;

a sensor, adapted to detect an indication of a physiological parameter of the subject; and

a wireless transmitter, adapted to wirelessly transmit the indication; and

an ingestible capsule, which comprises;

a wireless receiver, adapted to receive the indication;

first and second electrodes; and

a control component, adapted to facilitate passage of the drug through an epithelial layer of a gastrointestinal (GI) tract of the subject by driving the first and second electrodes to apply a series of pulses at a current of less than about 5 mA, at a frequency of between about 12 Hz and about 24 Hz, and with a pulse duration of between about 0.5 milliseconds and about 3 milliseconds.

96. The apparatus according to claim 95, wherein the indication includes an indication of blood pressure of the subject, and wherein the sensor is adapted to sense the indication of blood pressure.

97. The apparatus according to claim 95, wherein the indication includes an indication of a heart-related parameter of the subject, and wherein the sensor is adapted to sense the indication of the heart-related parameter.

98. The apparatus according to claim 95, wherein the indication includes an indication of a level of activity of the subject, and wherein the sensor is adapted to sense the indication of the level of activity.

99. The apparatus according to claim 95, wherein the indication includes an indication of a temperature of the subject, and wherein the sensor is adapted to sense the indication of the temperature.

100. The apparatus according to claim 95, wherein the indication includes an indication of a circadian cycle of the subject, and wherein the sensor comprises clock circuitry adapted to sense the indication of the circadian cycle.

101. The apparatus according to claim 95, wherein the control component is adapted to apply the series of pulses at a current of between about 2 mA and about 4 mA.

102. The apparatus according to claim 101, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a current of about 3 mA.

103. The apparatus according to claim 95, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a frequency of between about 16 Hz and about 20 Hz.

104. The apparatus according to claim 103, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a frequency of about 18 Hz.

105. The apparatus according to claim 95, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses with a pulse duration of between about 0.5 milliseconds and about 1.5 milliseconds.

106. The apparatus according to claim 105, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses with a pulse duration of about 1 millisecond.

107. The apparatus according to claim 95, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses for a period of between about 1 and about 360 minutes.

108. The apparatus according to claim 107, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses for a period of between about 60 and about 240 minutes.

109. Apparatus for facilitating administration of a drug to a subject, the apparatus comprising:

first and second electrodes; and

a control component, adapted to facilitate passage of the drug through an epithelial layer of a gastrointestinal (GI) tract of the subject by driving the first and second electrodes to apply a series of pulses at a current of less than about 5 mA, at a frequency of between about 12 Hz and about 24 Hz, and with a pulse duration of between about 0.5 milliseconds and about 3 milliseconds.

110. The apparatus according to claim 109, wherein the control component is adapted to apply the series of pulses at a current of between about 2 mA and about 4 mA.

111. The apparatus according to claim 110, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a current of about 3 mA.

112. The apparatus according to claim 109, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a frequency of between about 16 Hz and about 20 Hz.

113. The apparatus according to claim 112, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses at a frequency of about 18 Hz.

114. The apparatus according to claim 109, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses with a pulse duration of between about 0.5 milliseconds and about 1.5 milliseconds.

115. The apparatus according to claim 114, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses with a pulse duration of about 1 millisecond.

116. The apparatus according to claim 109, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses for a period of between about 1 and about 360 minutes.

117. The apparatus according to claim 116, wherein the control component is adapted to drive the first and second electrodes to apply the series of pulses for a period of between about 60 and about 240 minutes.

118. A method for administration of a drug, comprising:

administering to a subject an ingestible capsule that includes the drug;

detecting a disposition of the capsule within a gastrointestinal (GI) tract of the subject; and

in response to detecting the disposition, facilitating, by the capsule, passage of the drug through an epithelial layer of the GI tract, by applying a series of pulses at a current of less than about 5 mA, at a frequency of between about 12 Hz and about 24 Hz, and with a pulse duration of between about 0.5 milliseconds and about 3 milliseconds.

119. The method according to claim 118, wherein the pulses include monophasic rectangular pulses, and wherein applying the series of pulses comprises applying the series of monophasic rectangular pulses.

120. The method according to claim 118,

wherein detecting the disposition of the capsule comprises sensing an indication of a distance traveled by the capsule in the GI tract, and

wherein facilitating the passage of the drug comprises facilitating the passage responsive to the distance.

121. The method according to claim 118, wherein detecting the disposition of the capsule comprises imaging the GI tract, and wherein applying the series of pulses comprises applying the series of pulses in response to an acquired image.

122. The method according to claim 118, wherein the disposition of the capsule includes a temperature in a vicinity of the capsule, wherein detecting the disposition of the capsule comprises sensing the temperature, and wherein applying the series of pulses comprises applying the series of pulses in response to the sensed temperature.

123. The method according to claim 118, wherein the disposition of the capsule includes a pH in a vicinity of the capsule, wherein detecting the disposition of the capsule comprises sensing the pH, and wherein applying the series of pulses comprises applying the series of pulses in response to the sensed pH.

124. The method according to claim 118, wherein detecting the disposition of the capsule comprises sensing a characteristic of the GI tract, and wherein applying the series of pulses comprises applying the series of pulses in response to the sensed characteristic.

125. The method according to claim 118, wherein facilitating the passage of the drug comprises applying the series of pulses, and applying an iontophoretic current.

126. The method according to claim 118, wherein applying the series of pulses comprises configuring the series of pulses using parameters selected at least in part responsively to the disposition of the capsule within the GI tract.

127. The method according to claim 118, wherein applying the series of pulses comprises configuring the series of pulses using parameters selected at least in part responsively to a property of the drug.

128. The method according to claim 118, wherein applying the series of pulses comprises applying the series of pulses at a current of between about 2 mA and about 4 mA.

129. The method according to claim 128, wherein applying the series of pulses comprises applying the series of pulses at a current of about 3 mA.

130. The method according to claim 118, wherein applying the series of pulses comprises applying the series of pulses at a frequency of between about 16 Hz and about 20 Hz.

131. The method according to claim 130, wherein applying the series of pulses comprises applying the series of pulses at a frequency of about 18 Hz.

132. The method according to claim 118, wherein applying the series of pulses comprises applying the series of pulses with a pulse duration of between about 0.5 milliseconds and about 1.5 milliseconds.

133. The method according to claim 132, wherein applying the series of pulses comprises applying the series of pulses with a pulse duration of about 1 millisecond.

134. The method according to claim 118, wherein applying the series of pulses comprises applying the series of pulses for a period of between about 1 and about 360 minutes.

135. The method according to claim 134, wherein applying the series of pulses comprises applying the series of pulses for a period of between about 60 and about 240 minutes.

136. A method for administration of a drug contained in a pill, comprising:

orally administering the pill to a subject;

orally administering to the subject an ingestible capsule that does not include the drug;

detecting a target location of the capsule within a gastrointestinal (GI) tract of the subject; and

in response to detecting the target location, facilitating, by the capsule, passage of the drug through an epithelial layer of the GI tract, by applying a series of pulses at a current of less than about 5 mA, at a frequency of between about 12 Hz and about 24 Hz, and with a pulse duration of between about 0.5 milliseconds and about 3 milliseconds.

137. The method according to claim 136, wherein detecting the target location of the capsule comprises sensing an indication of a distance traveled by the housing in the GI tract.

138. The method according to claim 136, wherein detecting the target location of the capsule comprises imaging the GI tract, and detecting the target location responsive to an acquired image.

139. The method according to claim 136, wherein detecting the target location comprises sensing a characteristic of the GI tract.

140. The method according to claim 136, wherein applying the series of pulses comprises applying the series of pulses at a current of between about 2 mA and about 4 mA.

141. The method according to claim 140, wherein applying the series of pulses comprises applying the series of pulses at a current of about 3 mA.

142. The method according to claim 136, wherein applying the series of pulses comprises applying the series of pulses at a frequency of between about 16 Hz and about 20 Hz.

143. The method according to claim 142, wherein applying the series of pulses comprises applying the series of pulses at a frequency of about 18 Hz.

144. The method according to claim 136, wherein applying the series of pulses comprises applying the series of pulses with a pulse duration of between about 0.5 milliseconds and about 1.5 milliseconds.

145. The method according to claim 144, wherein applying the series of pulses comprises applying the series of pulses with a pulse duration of about 1 millisecond.

146. The method according to claim 136, wherein applying the series of pulses comprises applying the series of pulses for a period of between about 1 and about 360 minutes.

147. The method according to claim 146, wherein applying the series of pulses comprises applying the series of pulses for a period of between about 60 and about 240 minutes.

148. A method for administration of a drug, comprising:

coupling, to an ingestible capsule, a drug pill containing the drug;

administering the capsule to a subject;

detecting a target location of the capsule within a gastrointestinal (GI) tract of the subject; and

in response to detecting the target location, facilitating, by the capsule, passage of the drug through an epithelial layer of the GI tract, by applying a series of pulses at a current of less than about 5 mA, at a frequency of between about 12 Hz and about 24 Hz, and with a pulse duration of between about 0.5 milliseconds and about 3 milliseconds.

149. The method according to claim 148, wherein the drug pill includes a commercially-available drug pill, and wherein coupling comprises coupling the commercially-available drug pill to the ingestible capsule.

150. The method according to claim 148, wherein coupling comprises coupling the drug pill to the ingestible capsule using an adhesive.

151. The method according to claim 148, wherein applying the series of pulses comprises driving a current between at least two electrodes, and wherein coupling comprises coupling the drug pill to the ingestible capsule using at least one of the electrodes.

152. The method according to claim 151, wherein coupling using the at least one of the electrodes comprises positioning the at least one of the electrodes around a portion of the drug pill.

153. The method according to claim 148, wherein applying the series of pulses comprises applying the series of pulses at a current of between about 2 mA and about 4 mA.

154. The method according to claim 153, wherein applying the series of pulses comprises applying the series of pulses at a current of about 3 mA.

155. The method according to claim 148, wherein applying the series of pulses comprises applying the series of pulses at a frequency of between about 16 Hz and about 20 Hz.

156. The method according to claim 155, wherein applying the series of pulses comprises applying the series of pulses at a frequency of about 18 Hz.

157. The method according to claim 148, wherein applying the series of pulses comprises applying the series of pulses with a pulse duration of between about 0.5 milliseconds and about 1.5 milliseconds.

158. The method according to claim 157, wherein applying the series of pulses comprises applying the series of pulses with a pulse duration of about 1 millisecond.

159. The method according to claim 148, wherein applying the series of pulses comprises applying the series of pulses for a period of between about 1 and about 360 minutes.

160. The method according to claim 159, wherein applying the series of pulses comprises applying the series of pulses for a period of between about 60 and about 240 minutes.

161. A method for facilitating administration of a drug to a subject, the method comprising:

administering an ingestible capsule to the subject;

detecting an indication of a concentration of a substance in a blood circulation of the subject;

wirelessly transmitting the indication;

receiving the indication at the ingestible capsule; and

responsively to the received indication, facilitating, by the capsule, passage of the drug through an epithelial layer of a gastrointestinal (GI) tract of the subject, by applying a series of pulses at a current of less than about 5 mA, at a frequency of between about 12 Hz and about 24 Hz, and with a pulse duration of between about 0.5 milliseconds and about 3 milliseconds.

162. The method according to claim 161, wherein the substance includes the drug, and wherein detecting the indication of the concentration of the substance comprises detecting the indication of the concentration of the drug in the blood circulation.

163. The method according to claim 161,

wherein the substance includes a calibrating substance,

wherein detecting the indication of the concentration of the substance comprises detecting the indication of the concentration of the calibrating substance in the blood circulation, and

wherein facilitating the passage of the drug comprises facilitating passage of the calibrating substance and the drug through the epithelial layer of the GI tract, responsively to the received indication.

164. The method according to claim 161, wherein detecting the indication comprises noninvasively detecting the indication.

165. The method according to claim 161, wherein detecting the indication comprises invasively detecting the indication.

166. The method according to claim 161, wherein the ingestible capsule includes the drug, and wherein administering the ingestible capsule comprises administering the ingestible capsule that includes the drug.

167. The method according to claim 161, wherein administering the ingestible capsule comprises administering an ingestible capsule that does not contain the drug and that is not assembled in an integral unit with the drug.

168. The method according to claim 161, wherein the drug is contained in a drug pill, and wherein administering the ingestible capsule comprises coupling the drug pill to the ingestible capsule.

169. The method according to claim 161, comprising detecting a disposition of the ingestible capsule within the GI tract, wherein facilitating the passage of the drug comprises facilitating the passage in response to detecting the disposition.

170. The method according to claim 161,

wherein the indication includes respective first and second indications,

wherein detecting the indication comprises detecting the first and second indications at respective first and second times,

wherein transmitting the indication comprises wirelessly transmitting the first indication subsequent to the first time, and wirelessly transmitting the second indication subsequent to the second time, and

wherein applying the series of pulses comprises applying first and second series of pulses, responsive to the first and second indications.

171. The method according to claim 170, wherein applying the series of pulses comprises regulating at least one of the series of pulses responsive to at least one of the indications.

172. The method according to claim 170, wherein detecting the first and second indications at the respective first and second times comprises spacing the first and second times by at least 10 minutes.

173. The method according to claim 161, comprising wirelessly transmitting, by the capsule, a property of the capsule.

174. The method according to claim 173, wherein the property is selected from the list consisting of:

a location of the capsule, a status of the capsule, a pH of the GI tract, and a temperature of the GI tract, and wherein wirelessly transmitting the property comprises wirelessly transmitting, by the capsule, the selected property.

175. The method according to claim 161, wherein the substance includes a chemical, the blood concentration of which is affected by a blood concentration of the drug, and wherein detecting the indication of the concentration of the substance comprises detecting an indication of the concentration of the chemical in the blood circulation.

176. The method according to claim 175, wherein the chemical is selected from the list consisting of:

glucose, growth hormone, and hemoglobin-bound oxygen, and wherein detecting the indication of the concentration of the chemical comprises detecting the indication of the concentration of the selected chemical in the blood circulation.

177. The method according to claim 161, wherein applying the series of pulses comprises applying the series of pulses at a current of between about 2 mA and about 4 mA.

178. The method according to claim 177, wherein applying the series of pulses comprises applying the series of pulses at a current of about 3 mA.

179. The method according to claim 161, wherein applying the series of pulses comprises applying the series of pulses at a frequency of between about 16 Hz and about 20 Hz.

180. The method according to claim 179, wherein applying the series of pulses comprises applying the series of pulses at a frequency of about 18 Hz.

181. The method according to claim 161, wherein applying the series of pulses comprises applying the series of pulses with a pulse duration of between about 0.5 milliseconds and about 1.5 milliseconds.

182. The method according to claim 181, wherein applying the series of pulses comprises applying the series of pulses with a pulse duration of about 1 millisecond.

183. The method according to claim 161, wherein applying the series of pulses comprises applying the series of pulses for a period of between about 1 and about 360 minutes.

184. The method according to claim 183, wherein applying the series of pulses comprises applying the series of pulses for a period of between about 60 and about 240 minutes.

185. A method for facilitating administration of a drug to a subject, the method comprising:

administering an ingestible capsule to the subject;

detecting an indication of a physiological parameter of the subject;

wirelessly transmitting the indication;

receiving the indication at the ingestible capsule; and

responsively to the received indication, facilitating, by the capsule, passage of the drug through an epithelial layer of a gastrointestinal (GI) tract of the subject, by applying a series of pulses at a current of less than about 5 mA, at a frequency of between about 12 Hz and about 24 Hz, and with a pulse duration of between about 0.5 milliseconds and about 3 milliseconds.

186. The method according to claim 185, wherein the indication includes an indication of blood pressure of the subject, and wherein detecting the indication comprises detecting the indication of blood pressure.

187. The method according to claim 185, wherein the indication includes an indication of a heart-related parameter of the subject, and wherein detecting the indication comprises detecting the indication of the heart-related parameter.

188. The method according to claim 185, wherein the indication includes an indication of a level of activity of the subject, and wherein detecting the indication comprises detecting the indication of the level of activity.

189. The method according to claim 185, wherein the indication includes an indication of a circadian cycle of the subject, and wherein detecting the indication comprises detecting the indication of the circadian cycle.

190. The method according to claim 189, wherein the drug includes an antithrombotic drug, and wherein facilitating the passage of the drug comprises facilitating the passage of the antithrombotic drug through the epithelial layer.

191. The method according to claim 185, wherein the indication includes an indication of a temperature of the subject, and wherein detecting the indication comprises detecting the indication of the temperature.

192. The method according to claim 191, wherein the drug includes an antibiotic, and wherein facilitating the passage of the drug comprises facilitating the passage of the antibiotic through the epithelial layer.

193. The method according to claim 185, wherein applying the series of pulses comprises applying the series of pulses at a current of between about 2 mA and about 4 mA.

194. The method according to claim 193, wherein applying the series of pulses comprises applying the series of pulses at a current of about 3 mA.

195. The method according to claim 185, wherein applying the series of pulses comprises applying the series of pulses at a frequency of between about 16 Hz and about 20 Hz.

196. The method according to claim 195, wherein applying the series of pulses comprises applying the series of pulses at a frequency of about 18 Hz.

197. The method according to claim 185, wherein applying the series of pulses comprises applying the series of pulses with a pulse duration of between about 0.5 milliseconds and about 1.5 milliseconds.

198. The method according to claim 197, wherein applying the series of pulses comprises applying the series of pulses with a pulse duration of about 1 millisecond.

199. The method according to claim 185, wherein applying the series of pulses comprises applying the series of pulses for a period of between about 1 and about 360 minutes.

200. The method according to claim 199, wherein applying the series of pulses comprises applying the series of pulses for a period of between about 60 and about 240 minutes.

201. A method for administration of a drug, comprising:

administering the drug to a gastrointestinal (GI) tract of a subject; and

facilitating passage of the drug through an epithelial layer of the GI tract by applying a series of pulses at a current of less than about 5 mA, at a frequency of between about 12 Hz and about 24 Hz, and with a pulse duration of between about 0.5 milliseconds and about 3 milliseconds.

202. The method according to claim 201, wherein applying the series of pulses comprises applying the series of pulses at a current of between about 2 mA and about 4 mA.

203. The method according to claim 202, wherein applying the series of pulses comprises applying the series of pulses at a current of about 3 mA.

204. The method according to claim 201, wherein applying the series of pulses comprises applying the series of pulses at a frequency of between about 16 Hz and about 20 Hz.

205. The method according to claim 204, wherein applying the series of pulses comprises applying the series of pulses at a frequency of about 18 Hz.

206. The method according to claim 201, wherein applying the series of pulses comprises applying the series of pulses with a pulse duration of between about 0.5 milliseconds and about 1.5 milliseconds.

207. The method according to claim 206, wherein applying the series of pulses comprises applying the series of pulses with a pulse duration of about 1 millisecond.

208. The method according to claim 201, wherein applying the series of pulses comprises applying the series of pulses for a period of between about 1 and about 360 minutes.

209. The method according to claim 208, wherein applying the series of pulses comprises applying the series of pulses for a period of between about 60 and about 240 minutes.