Pharmaceutical dosage form and method of making

• US 20040081689A1
• Filed: 10/24/2002
• Published: 04/29/2004
• Est. Priority Date: 10/24/2002
• Status: Abandoned Application

• Current Assignee: Hewlett-Packard Development Company, L.P. (HP Inc.)
• Original Assignee: Hewlett-Packard Development Company, L.P. (HP Inc.)
• Inventors: Dunfield, John Stephen, Ayres, James W.
• Application Number:
  US10/280,692
• Publication Number:
  US 20040081689A1
• Time in Patent Office: Days
• US Class Current: 424/451
• CPC Class Codes: A61J 3/00 Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
• CPC Class Codes: A61J 3/07 into the form of capsules or similar small containers for oral use
• CPC Class Codes: A61J 3/074 Filling capsules; Related operations
• CPC Class Codes: A61K 51/1282 Devices used in vivo and carrying the radioactive therapeutic or diagnostic agent, therapeutic or in vivo diagnostic kits, stents
• 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: A61K 9/4833 Encapsulating processes; Filling of capsules mechanical aspects A61J3/07
• CPC Class Codes: A61P 3/02 Nutrients, e.g. vitamins, minerals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: B41J 2/04 generating single droplets or particles on demand

Abstract

A pharmaceutical dosage form including an enclosing medium having an interior surface including at least one discrete deposit of a bioactive substance dispensed on the interior surface of the enclosing medium.

Claims

1. A method of making a pharmaceutical dosage form, comprising:

inserting a fluid ejector body into an opening of an enclosing medium; and

activating a fluid ejector actuator to eject a bioactive fluid onto at least a portion of an interior surface of said enclosing medium at controlled locations on said interior surface.

2. The method in accordance with the method of claim 1, wherein inserting a fluid ejector body further comprises inserting a fluid ejector body into an opening of a capsule.

3. The method in accordance with the method of claim 2, wherein said capsule has a diameter in the range from about 3 millimeters to about 12 millimeters.

4. The method in accordance with the method of claim 1, wherein activating said fluid ejector actuator further comprises dispensing said bioactive fluid substantially perpendicular to said interior surface of said enclosing medium.

5. The method in accordance with the method of claim 1, wherein activating said fluid ejector actuator further comprises dispensing said bioactive fluid in a predetermined angle to the surface normal of said enclosing medium.

6. The method in accordance with the method of claim 5, wherein said predetermined angle is in the range from about minus sixty degrees to plus sixty degrees about the surface normal of said enclosing medium.

7. The method in accordance with the method of claim 5, wherein said predetermined angle is in the range from about minus forty five degrees to plus forty five degrees about the surface normal of said enclosing medium.

8. The method in accordance with the method of claim 5, further comprising printing information onto said enclosing medium.

9. The method in accordance with the method of claim 8, wherein printing said information further comprises printing manufacturing information onto said enclosing medium.

10. The method in accordance with the method of claim 9, wherein printing said manufacturing information further comprises printing said manufacturing information onto said enclosing medium in a machine understood form.

11. The method in accordance with the method of claim 9, wherein printing said manufacturing information further comprises printing said manufacturing information onto said enclosing medium in a human-perceptible form.

12. The method in accordance with the method of claim 8, wherein printing said information further comprises ejecting an ingestible ink from at least one ink ejector onto at least a portion of said interior surface of said enclosing medium.

13. The method in accordance with the method of claim 12, wherein ejecting said ingestible ink further comprises ejecting said ingestible ink onto at least a portion of said interior surface of a capsule.

14. The method in accordance with the method of claim 8, wherein printing said information further comprises printing patient information onto said enclosing medium.

15. The method in accordance with the method of claim 1, further comprises sealing said dispensed bioactive substance on said enclosing medium.

16. The method in accordance with the method of claim 15, wherein sealing said dispensed bioactive substance further comprises activating a sealant fluid ejector to eject a barrier component fluid over said dispensed bioactive substance.

17. The method in accordance with the method of claim 16, wherein said barrier component fluid reacts with said dispensed bioactive substance.

18. The method in accordance with the method of claim 16, wherein said bioactive active fluid further comprises at least one solvent component, wherein said barrier component fluid reacts with said at least one solvent component.

19. The method in accordance with the method of claim 1, wherein activating said fluid ejector actuator further comprises activating a fluid energy generating element a predetermined number of times n to eject essentially n drops of said bioactive fluid onto said interior surface of said enclosing medium.

20. The method in accordance with the method of claim 19, wherein activating said fluid energy generating element further comprises dispensing said bioactive fluid in a two-dimensional array forming an areal density of bioactive agent deposits onto said enclosing medium.

21. The method in accordance with the method of claim 20, further comprising:

activating a sealant fluid ejector to eject a barrier component over said areal density of said bioactive agent deposits;

repeating said activating said fluid energy generating element and said activating said sealant fluid ejector multiple times to generate a three-dimensional array of bioactive agent deposits on said enclosing medium.

22. The method in accordance with the method of claim 1, further comprising:

inserting an insert fluid ejector body into an opening of an enclosing insert medium having a radial direction;

activating an insert fluid ejector actuator to eject an insert bioactive fluid onto at least a portion of an interior surface of said enclosing insert medium; and

telescoping said enclosing insert medium into said opening of said enclosing medium.

23. The method in accordance with the method of claim 22, wherein activating said insert fluid ejector further comprises dispensing said insert bioactive fluid in an insert two-dimensional array forming an insert areal density of insert bioactive agent deposits onto said enclosing insert medium.

24. The method in accordance with the method of claim 23, wherein activating said fluid ejector actuator further comprises activating a fluid energy generating element, dispensing said bioactive fluid in a two-dimensional array, forming an areal density of bioactive agent deposits onto said enclosing medium, and wherein said insert areal density of said insert bioactive agent deposits forms a bioactive agent gradient in said radial direction of said enclosing insert medium.

25. The method in accordance with the method of claim 24, wherein said bioactive agent gradient is adapted to provide a dosage form wherein after being ingested the amount of said bioactive substance released increases over time.

26. The method in accordance with the method of claim 24, wherein said bioactive agent gradient is adapted to provide a dosage form wherein after being ingested the amount of said bioactive substance released decreases over time.

27. The method in accordance with the method of claim 24, wherein said bioactive agent gradient is adapted to provide a dosage form wherein after being ingested the amount of said bioactive substance released remains constant over time.

28. The method in accordance with the method of claim 24, wherein said bioactive agent gradient is adapted to provide a dosage form wherein after being ingested the amount of said bioactive substance released is pulsed at uniform times.

29. The method in accordance with the method of claim 24, wherein said bioactive agent gradient is adapted to provide a dosage form wherein after being ingested a discrete amount of said bioactive substance released is pulsed at varying times.

30. A pharmaceutical dosage form produced by the method of claim 24.

31. The method in accordance with the method of claim 22, wherein activating said insert fluid ejector actuator further comprises activating a second insert fluid ejector actuator to dispense a second insert bioactive fluid onto said enclosing insert medium.

32. The method in accordance with the method of claim 22, wherein said second bioactive fluid is deposited onto said interior surface of said enclosing insert medium.

33. The method in accordance with the method of claim 22, wherein telescoping said enclosing insert medium further comprises telescoping a plurality of enclosing insert mediums into said enclosing medium.

34. A pharmaceutical dosage form produced by the method of claim 33.

35. A pharmaceutical dosage form produced by the method of claim 1.

36. The method in accordance with the method of claim 1, wherein activating said fluid ejector actuator further comprises activating a fluid energy generating element depositing essentially a drop of said bioactive fluid onto said interior surface of said enclosing medium for each activation of said fluid energy generating element.

37. The method in accordance with the method of claim 36, wherein said drop is in the range from about five femtoliters to about one microliter.

38. The method in accordance with the method of claim 36, wherein said drop is in the range from about five femtoliters to about ten nanoliters.

39. The method in accordance with the method of claim 1 wherein activating said fluid ejector actuator further comprises activating said fluid ejector actuator to dispense said bioactive fluid in overlapping deposits forming essentially a layer of bioactive substance deposits.

40. The method in accordance with the method of claim 1, wherein activating said fluid ejector actuator further comprises activating a second fluid ejector to dispense at least a drop of a second bioactive fluid onto said interior surface of said enclosing medium.

41. The method in accordance with the method of claim 1, wherein activating said fluid ejector actuator further comprises activating said fluid ejector actuator to dispense a mixture of said bioactive fluid and an ingestible ink.

42. The method in accordance with the method of claim 1, wherein activating said fluid ejector actuator further comprises activating said fluid ejector actuator to eject a radioactive fluid, said radioactive fluid including a radioactive isotope.

43. The method in accordance with the method of claim 42, wherein said radioactive isotope is selected from the group consisting of palladium-103, iodine-125, gold-199, ytrium-90 iridium-192, americium-241, and combinations thereof

44. A brachytherapy device produced by the method of claim 42.

45. A pharmaceutical dosage form comprising:

an enclosing medium having an interior surface including at least one discrete deposit of a bioactive substance dispensed on said interior surface of said enclosing medium.

46. The pharmaceutical dosage form in accordance with claim 45, wherein said enclosing medium is a capsule.

47. The pharmaceutical dosage form in accordance with claim 46, wherein said capsule has an outer diameter in the range from about 3 millimeters to about 12 millimeters.

48. The pharmaceutical dosage form in accordance with claim 45, wherein said at least one discrete deposit further comprises a two dimensional array of discrete deposits of said bioactive substance.

49. The pharmaceutical dosage form in accordance with claim 45, further comprising printed information on said enclosing medium.

50. The pharmaceutical dosage form in accordance with claim 49, wherein said printed information further comprises printed information on said interior surface of said enclosing medium.

51. The pharmaceutical dosage form in accordance with claim 50, wherein said enclosing medium is a capsule.

52. The pharmaceutical dosage form in accordance with claim 50, wherein said printed information further comprises printed manufacturing information.

53. The pharmaceutical dosage form in accordance with claim 50, wherein said printed information further comprises printed information in a machine understood form.

54. The pharmaceutical dosage form in accordance with claim 50, wherein said printed information further comprises printed information in a human-perceptible form.

55. The pharmaceutical dosage form in accordance with claim 45, further comprising a sealant material deposited over said at least one discrete deposit of said bioactive substance.

56. The pharmaceutical dosage form in accordance with claim 55, wherein said sealant material further comprises a sealant material having a density less than about 1.0 gram per milliliter, wherein said enclosing medium is adapted to float.

57. The pharmaceutical dosage form in accordance with claim 45, further comprising at least one insert medium having at least one insert discrete deposit of said bioactive substance dispensed on either an interior surface or an outer surface of said at least one insert medium.

58. The pharmaceutical dosage form in accordance with claim 57, wherein said at least one insert medium is telescoped into said enclosing medium.

59. The pharmaceutical dosage form in accordance with claim 57, wherein said at least one insert discrete deposit further comprises a two dimensional array of insert discrete deposits of said bioactive substance.

60. The pharmaceutical dosage form in accordance with claim 59, wherein said at least one discrete deposit of said bioactive substance on said interior surface of said enclosing medium further comprises a two-dimensional array of discrete deposits of said bioactive substance on said interior surface of said enclosing medium, and said two-dimensional array of insert discrete deposits forms a bioactive substance gradient in a radial direction of said enclosing medium.

61. The pharmaceutical dosage form in accordance with claim 60, wherein said bioactive substance gradient is adapted to release an increasing amount of said bioactive substance over time, after being ingested.

62. The pharmaceutical dosage form in accordance with claim 60, wherein said bioactive substance gradient is adapted to release a decreasing amount of said bioactive substance over time, after being ingested.

63. The pharmaceutical dosage form in accordance with claim 60, wherein said bioactive substance gradient is adapted to release a constant amount of said bioactive substance over time, after being ingested.

64. The pharmaceutical dosage form in accordance with claim 60, wherein said bioactive substance gradient is adapted to release a pulsed amount of said bioactive substance over time, after being ingested.

65. The pharmaceutical dosage form in accordance with claim 60, wherein said bioactive substance gradient is adapted to release a discrete amount of said bioactive substance over time, after being ingested.

66. The pharmaceutical dosage form in accordance with claim 45, further comprising multiple discrete deposits of multiple bioactive substances dispensed on said interior surface of said enclosing medium.

67. The pharmaceutical dosage form in accordance with claim 45, wherein said bioactive substance further comprises a mixture of said bioactive substance and an ingestible ink.

68. The pharmaceutical dosage form in accordance with claim 45, wherein said at least one discrete deposit of said bioactive substance further comprises at least one microparticulate deposit weighing in the range from about 1 picogram to about 10 micrograms.

69. The pharmaceutical dosage form in accordance with claim 45, wherein said at least one discrete deposit of said bioactive substance further comprises at least one microparticulate deposit weighing in the range from about 1 picogram to about 1 milligrams.

70. The pharmaceutical dosage form in accordance with claim 45, wherein said enclosing medium further comprises a substantially insoluble material adapted to provide diffusion of a liquid through said substantially insoluble material from an outer surface of said enclosing medium to said interior surface.

71. The pharmaceutical dosage form in accordance with claim 45, wherein said enclosing medium further comprises at least one perforation through said enclosing medium providing entry of a liquid to said interior surface of said enclosing medium.

72. The pharmaceutical dosage form in accordance with claim 45, wherein said enclosing medium is coated to promote dissolution.

73. The pharmaceutical dosage form in accordance with claim 45, wherein said enclosing medium is coated to resist dissolution.

74. The pharmaceutical dosage form in accordance with claim 45, further comprising an inside liner material deposited on said interior surface of said enclosing medium.

75. The pharmaceutical dosage form in accordance with claim 74, wherein said inside liner materials is a difusional resistant membrane.

76. The pharmaceutical dosage form in accordance with claim 74, wherein said inside liner materials is a enteric coating membrane.

77. The pharmaceutical dosage form in accordance with claim 45, wherein said bioactive substance is a radioactive material.

78. The pharmaceutical dosage form in accordance with claim 77, wherein said radioactive material is selected from the group consisting of palladium-103, iodine-125, gold-199, ytrium-90 iridium-192, americium-241, and combinations thereof.

79. A pharmaceutical dosage form comprising:

an enclosing medium having an interior surface; and

means for generating at least one discrete deposit of a bioactive agent on said interior surface of said enclosing medium.

80. The pharmaceutical dosage form in accordance with claim 79, wherein said means for generating at least one discrete deposit further comprises means for generating a two-dimensional array of discrete deposits of said bioactive substance on said interior surface of said enclosing medium.

81. The pharmaceutical dosage form in accordance with claim 80, wherein said means for generating a two-dimensional array further comprises means for creating a bioactive substance gradient in a radial direction of said enclosing medium.

82. The pharmaceutical dosage form in accordance with claim 79, further comprises means for printing information on said interior surface of said enclosing medium.

83. The pharmaceutical dosage form in accordance with claim 79, wherein said means for generating at least one discrete deposit further comprises means for forming at least one microparticulate deposit of the bioactive substance on said interior surface of said enclosing medium, wherein said at least one microparticulate deposit weighs in the range from about 1 picogram to about 10 micrograms.

84. A bioactive fluid ejector head comprising:

a fluid ejector body adapted to be inserted into an opening of a pharmaceutical enclosing medium, said pharmaceutical enclosing medium having an interior surface;

at least one nozzle disposed on said fluid ejector body;

a fluid ejector actuator in fluid communication with said at least one nozzle, wherein activation of said fluid ejector actuator ejects a bioactive fluid through said at least one nozzle onto a discrete predetermined location on said interior surface of said pharmaceutical enclosing medium.

85. The bioactive fluid ejector head in accordance with claim 84, wherein said fluid ejector actuator further comprises a fluid energy generating element, wherein activation of said fluid energy generating element ejects essentially a drop of said bioactive fluid onto said discrete predetermined location on said interior surface of said pharmaceutical enclosing medium.

86. A bioactive fluid dispensing system comprising:

at least one bioactive fluid ejector head of claim 84;

a fluid controller operably coupled to said fluid ejector actuator; and

at least one enclosing medium holder adapted to hold said pharmaceutical enclosing medium, wherein said fluid controller activates said fluid ejector actuator to eject a bioactive fluid onto said interior surface of said pharmaceutical enclosing medium.

87. The fluid dispensing system in accordance with claim 86, wherein said at least one fluid ejection cartridge further comprises an i×

j array of fluid ejector heads, and said at least one enclosing medium holder further comprises an enclosing medium tray having an n×

m array of enclosing medium holders.

88. The fluid dispensing system in accordance with claim 86, wherein said enclosing medium holder further comprises an enclosing medium rotator, said enclosing medium rotator rotates said interior surface of said pharmaceutical enclosing medium around an enclosing medium longitudinal axis.

89. The fluid dispensing system in accordance with claim 86, wherein said enclosing medium holder and said fluid controller dispense said bioactive fluid in a two-dimensional array onto said interior surface of said pharmaceutical enclosing medium.

90. The fluid dispensing system in accordance with claim 86, further comprising:

a transport mechanism coupled to said at least one enclosing medium holder providing movement to said at least one enclosing medium holder;

a transport controller operably coupled to said transport mechanism providing signals to control movement of said at least one enclosing medium holder in three mutually orthogonal directions, and wherein said transport controller provides a rotational signal to said transport mechanism to rotate an enclosing medium tray about a central axis.

91. The fluid dispensing system in accordance with claim 86, further comprising an inspection unit providing in-line non-destructive testing of said pharmaceutical enclosing medium.