Abuse resistant oral opioid formulations

1. An oral, extended release pharmaceutical composition in tablet form configured to deter abuse, comprising:

an inner expansion layer that does not contain any drug and comprises a hydrophilic expandable polymer that forms a gel when exposed to a liquid comprising water and/or alcohol, wherein the expandable polymer is selected from the group consisting of methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, hydroxypropylmethylcellulose, alginic acid, tragacanth, and combinations thereof;

a barrier layer that substantially covers the expansion layer, wherein the barrier layer comprises a first polymer selected from the group consisting of: acrylic or methacrylic polymers or copolymers thereof, wherein when the pharmaceutical composition is administered in intact form, the first polymer of the barrier layer is substantially undissolved in the gastrointestinal (GI) tract; and

a diffusion layer covering the barrier layer, the diffusion layer comprising a drug comprising an opioid in a pharmaceutically effective amount and a second polymer selected from the group consisting of: acrylic or methacrylic polymers or copolymers thereof, wherein the drug is substantially homogeneously distributed within the second polymer and diffuses from the diffusion layer within the GI tract, wherein the diffusion layer is bonded to the barrier layer by curing the layers together, wherein the pharmaceutical composition does not comprise a drug that is not an opioid agonist or a central nervous system stimulant, and wherein the diffusion layer is the only drug-containing layer in the pharmaceutical composition,

wherein the second polymer is present in an amount sufficient to release at least 50% of the amount of drug after 8 hours after administration in intact form,

wherein the first polymer and second polymer each comprise the same polymer,

and wherein when the pharmaceutical composition is orally or intranasally administered in crushed form to a subject, the Cmax/AUC achieved 8 hours after administration is lower than the Cmax/AUC achieved 8 hours after administration of a crushed bioequivalent composition not configured to deter abuse.

2. An oral, extended release pharmaceutical composition in tablet form configured to deter abuse, comprising:

an inner expansion layer that does not contain any drug and comprises a hydrophilic expandable polymer that forms a gel when exposed to a liquid comprising water and/or alcohol, wherein the expandable polymer is selected from the group consisting of methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, hydroxypropylmethylcellulose, alginic acid, tragacanth, and combinations thereof;

a barrier layer that substantially covers the expansion layer, wherein the barrier layer comprises a first polymer selected from the group consisting of: acrylic or methacrylic polymers or copolymers thereof, wherein when the pharmaceutical composition is administered in intact form, the first polymer of the barrier layer is substantially undissolved in the gastrointestinal (GI) tract; and

a diffusion layer covering the barrier layer, the diffusion layer comprising a drug comprising an opioid in a pharmaceutically effective amount and a second polymer selected from the group consisting of: acrylic or methacrylic polymers or copolymers thereof, wherein the drug is substantially homogenously distributed within the second polymer and diffuses from the diffusion layer within the GI tract,

wherein the diffusion layer is bonded to the barrier layer by curing the layers together, wherein the pharmaceutical composition does not comprise a drug that is not an opioid agonist or a central nervous system stimulant, and wherein the diffusion layer is the only drug-containing layer in the pharmaceutical composition,

wherein the second polymer is present in an amount sufficient to release at least 50% of the amount of drug after 8 hours after administration in intact form,

wherein the first polymer and second polymer each comprise the same polymer, and

wherein when the pharmaceutical composition is orally or intranasally administered in crushed form to a subject, the Cmax and/or AUC achieved 8 hours after administration is lower than the Cmax and/or AUC achieved 8 hours after administration of a crushed bioequivalent composition not configured to deter abuse.

3. An oral, extended release pharmaceutical composition in tablet form configured to deter abuse, comprising:

an inner expansion layer that does not contain any drug and comprises a hydrophilic expandable polymer that forms a gel when exposed to a liquid comprising water and/or alcohol, wherein the expandable polymer is selected from the group consisting of methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, hydroxypropylmethylcellulose, alginic acid, tragacanth, and combinations thereof;

a barrier layer that substantially covers the expansion layer, wherein the barrier layer comprises a first polymer selected from the group consisting of: acrylic or methacrylic polymers or copolymers thereof, wherein when the pharmaceutical composition is administered in intact form, the first polymer of the barrier layer is substantially undissolved in the gastrointestinal (GI) tract; and

a diffusion layer covering the barrier layer, the diffusion layer comprising a drug comprising an opioid in a pharmaceutically effective amount and a second polymer selected from the group consisting of: acrylic or methacrylic polymers or copolymers thereof, wherein the drug is substantially homogeneously distributed within the second polymer and diffuses from the diffusion layer within the GI tract, wherein the diffusion layer is bonded to the barrier layer by curing the layers together, wherein the pharmaceutical composition does not comprise a drug that is not an opioid agonist or a central nervous system stimulant, and wherein the diffusion layer is the only drug-containing layer in the pharmaceutical composition,

wherein the second polymer is present in an amount sufficient to release at least 50% of the amount of drug after 8 hours after administration in intact form,

wherein the first polymer and second polymer each comprise the same polymer, and

wherein when the pharmaceutical composition is orally administered in crushed form to a subject, the rate of drug released from the composition at 4 hours after administration is substantially the same or lower than the rate of drug released 4 hours after administration of when the pharmaceutical composition is administered in intact form.

4. An oral, extended release pharmaceutical composition in tablet form configured to deter abuse, comprising:

an inner expansion layer that does not contain any drug and comprises a hydrophilic expandable polymer that forms a gel when exposed to a liquid comprising water and/or alcohol, wherein the expandable polymer is selected from the group consisting of methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, hydroxypropylmethylcellulose, alginic acid, tragacanth, and combinations thereof;

a barrier layer that substantially covers the expansion layer, wherein the barrier layer comprises a first polymer selected from the group consisting of: acrylic or methacrylic polymers or copolymers thereof, wherein when the pharmaceutical composition is administered in intact form, the first polymer of the barrier layer is substantially undissolved in the gastrointestinal (GI) tract; and

a diffusion layer covering the barrier layer, the diffusion layer comprising a drug comprising an opioid in a pharmaceutically effective amount and a second polymer selected from the group consisting of: acrylic or methacrylic polymers or copolymers thereof, wherein the drug is substantially homogeneously distributed within the second polymer and diffuses from the diffusion layer within the GI tract, wherein the diffusion layer is bonded to the barrier layer by curing the layers together, wherein the pharmaceutical composition does not comprise a drug that is not an opioid agonist or a central nervous system stimulant, and wherein the diffusion layer is the only drug-containing layer in the pharmaceutical composition,

wherein the second polymer is present in an amount sufficient to release at least 50% of the amount of drug after 8 hours after administration in intact form,

wherein the first polymer and second polymer each comprise the same polymer, and

wherein when the pharmaceutical composition is orally administered in crushed form to a subject, the amount of drug released from the composition 8 hours after administration is substantially the same or lower than the amount of drug released 8 hours after administration of the pharmaceutical composition in intact form.

5. The pharmaceutical composition of claim 4 , wherein when the pharmaceutical composition is administered in crushed form to a subject, the amount of drug released from the composition at 8 hours after administration is no more than 75% of the amount of drug released at 8 hours after administration of the pharmaceutical composition in intact form.

6. An oral, extended release pharmaceutical composition in tablet form configured to deter abuse, comprising:

an inner expansion layer that does not contain any drug and comprises a hydrophilic expandable polymer that forms a gel when exposed to a liquid comprising water and/or alcohol, wherein the expandable polymer is selected from the group consisting of: methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, hydroxypropylmethylcellulose, alginic acid, tragacanth, and combinations thereof;

a barrier layer that substantially covers the expansion layer, wherein the barrier layer comprises a first polymer selected from the group consisting of: acrylic or methacrylic polymers or copolymers thereof, wherein when the pharmaceutical composition is administered in intact form, the first polymer of the barrier layer is substantially undissolved in the gastrointestinal (GI) tract; and

a diffusion layer covering the barrier layer, the diffusion layer comprising a drug comprising an opioid in a pharmaceutically effective amount and a second polymer selected from the group consisting of: acrylic or methacrylic polymers or copolymers thereof, wherein the drug is substantially homogeneously distributed within the second polymer and diffuses from the diffusion layer within the GI tract,

wherein the diffusion layer is bonded to the barrier layer by curing the layers together, wherein the pharmaceutical composition does not comprise a drug that is not an opioid agonist or a central nervous system stimulant, and wherein the diffusion layer is the only drug-containing layer in the pharmaceutical composition,

wherein the second polymer is present in an amount sufficient to release at least 50% of the amount of drug after 8 hours after administration in intact form,

wherein the first polymer and second polymer each comprise the same polymer, and

wherein when the pharmaceutical composition is orally administered in intact form, at least 50% of the amount of drug is released after 8 hours after administration and when the pharmaceutical composition is administered in crushed form no more than 40% of the amount of drug is released after 1 hour after administration.

7. The pharmaceutical composition of claim 6 , wherein when the pharmaceutical composition is administered in crushed form no more than 35% of the amount of drug is released in 15 minutes after administration.

8. An oral, immediate release pharmaceutical composition in tablet dosage form, comprising:

an inner expansion layer that does not contain any drug and comprises a hydrophilic expandable polymer that forms a gel when exposed to a liquid comprising water and/or alcohol, wherein the expandable polymer is selected from the group consisting of methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, hydroxypropylmethylcellulose, alginic acid, tragacanth, and combinations thereof;

a barrier layer that substantially covers the expansion layer, wherein the barrier layer comprises a first polymer selected from the group consisting of: acrylic or methacrylic polymers or copolymers thereof, wherein when the pharmaceutical composition is administered in intact form, the first polymer of the barrier layer is substantially undissolved in the gastrointestinal (GI) tract; and

a diffusion layer covering the barrier layer, the diffusion layer comprising a drug comprising an opioid in a pharmaceutically effective amount and a second polymer selected from the group consisting of: acrylic or methacrylic polymers or copolymers thereof, wherein the drug is homogeneously distributed within the second polymer and diffuses from the diffusion layer within the GI tract,

wherein the diffusion layer is bonded to the barrier layer by curing the layers together,

wherein the second polymer is present in an amount sufficient to release at least 90% of the amount of drug in 1 hour after administration in intact form,

wherein the first polymer and second polymer each comprise the same polymer,

wherein the pharmaceutical composition does not comprise a drug that is not an opioid agonist or a central nervous system stimulant, and wherein the diffusion layer is the only drug-containing layer in the pharmaceutical composition, and

wherein when the pharmaceutical composition is orally administered in intact form, at least 90% of the amount of drug is released in 1 hour after administration, and when the pharmaceutical composition is orally administered in crushed form, no more than 75% of the amount of drug is released in 1 hour after administration.

9. An oral, extended release pharmaceutical composition in tablet form configured to deter abuse, comprising:

an inner expansion layer that does not contain any drug and comprises a hydrophilic expandable polymer that forms a gel when exposed to a liquid comprising water and/or alcohol, wherein the expandable polymer is selected from the group consisting of methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, hydroxypropylmethylcellulose, alginic acid, tragacanth, and combinations thereof;

a barrier layer that substantially covers the expansion layer, wherein the barrier layer comprises a first polymer selected from the group consisting of: acrylic or methacrylic polymers or copolymers thereof, wherein when the pharmaceutical composition is administered in intact form, the first polymer of the barrier layer is substantially undissolved in the gastrointestinal (GI) tract; and

a diffusion layer covering the barrier layer, the diffusion layer comprising a drug comprising an opioid in an amount capable of producing euphoria and a second polymer selected from the group consisting of: acrylic or methacrylic polymers or copolymers thereof, wherein the diffusion layer is bonded to the barrier layer by curing the layers together, wherein the a drug is substantially homogeneously distributed within the second polymer and diffuses from the diffusion layer within the GI tract, wherein the diffusion layer is the only drug-containing layer in the pharmaceutical composition,

wherein the second polymer is present in an amount sufficient to release at least 50% of the amount of drug after 8 hours after administration in intact form,

wherein the first polymer and second polymer each comprise the same polymer, and

wherein when the pharmaceutical composition is administered in intact form to a subject, at least 50% of the amount of drug is released after 8 hours after administration, and wherein when the pharmaceutical composition is administered in crushed form to a subject, no more than 40% of the amount of drug is released in 1 hour after administration, and the intensity of the euphoria is lower than the intensity of the euphoria achieved after administration of a crushed bioequivalent composition not comprising a barrier layer comprising a first polymer and a diffusion layer comprising drug and a second polymer,

wherein the pharmaceutical composition does not comprise a drug that is not an opioid agonist, zaleplon, or a central nervous system stimulant.

10. The pharmaceutical composition of claim 1 , wherein the expandable polymer comprises hydroxypropylmethylcellulose.

11. The pharmaceutical composition of claim 1 , wherein the expandable polymer comprises hydroxypropylmethylcellulose, the first polymer is a copolymer of ethyl acrylate and methyl methacrylate, and the second polymer is a copolymer of ethyl acrylate and methyl methacrylate.

12. The pharmaceutical composition of claim 1 , wherein the drug is morphine.

13. The pharmaceutical composition of claim 1 , wherein the drug is oxycodone.

14. The pharmaceutical composition of claim 1 , wherein the drug is oxymorphone.

15. The pharmaceutical composition of claim 1 , wherein the drug is hydrocodone.

16. The pharmaceutical composition of claim 1 , wherein the drug is hydromorphone.

17. The pharmaceutical composition of claim 2 , wherein the expandable polymer comprises hydroxypropylmethylcellulose.

18. The pharmaceutical composition of claim 2 , wherein the expandable polymer comprises hydroxypropylmethylcellulose, the first polymer is a copolymer of ethyl acrylate and methyl methacrylate, and the second polymer is a copolymer of ethyl acrylate and methyl methacrylate.

19. The pharmaceutical composition of claim 2 , wherein the drug is morphine.

20. The pharmaceutical composition of claim 2 , wherein the drug is oxycodone.

21. The pharmaceutical composition of claim 2 , wherein the drug is oxymorphone.

22. The pharmaceutical composition of claim 2 , wherein the drug is hydrocodone.

23. The pharmaceutical composition of claim 2 , wherein the drug is hydromorphone.

24. The pharmaceutical composition of claim 3 , wherein the expandable polymer comprises hydroxypropylmethylcellulose.

25. The pharmaceutical composition of claim 3 , wherein wherein the expandable polymer comprises hydroxypropylmethylcellulose, the first polymer is a copolymer of ethyl acrylate and methyl methacrylate, and the second polymer is a copolymer of ethyl acrylate and methyl methacrylate.

26. The pharmaceutical composition of claim 3 , wherein the drug is morphine.

27. The pharmaceutical composition of claim 3 , wherein the drug is oxycodone.

28. The pharmaceutical composition of claim 3 , wherein the drug is oxymorphone.

29. The pharmaceutical composition of claim 3 , wherein the drug is hydrocodone.

30. The pharmaceutical composition of claim 3 , wherein the drug is hydromorphone.

31. The pharmaceutical composition of claim 4 , wherein the expandable polymer comprises hydroxypropylmethylcellulose.

32. The pharmaceutical composition of claim 4 , wherein the expandable polymer comprises hydroxypropylmethylcellulose, the first polymer is a copolymer of ethyl acrylate and methyl methacrylate, and the second polymer is a copolymer of ethyl acrylate and methyl methacrylate.

33. The pharmaceutical composition of claim 4 , wherein the drug is morphine.

34. The pharmaceutical composition of claim 4 , wherein the drug is oxycodone.

35. The pharmaceutical composition of claim 4 , wherein the drug is oxymorphone.

36. The pharmaceutical composition of claim 4 , wherein the drug is hydrocodone.

37. The pharmaceutical composition of claim 4 , wherein the drug is hydromorphone.

38. The pharmaceutical composition of claim 6 , wherein the expandable polymer comprises hydroxypropylmethylcellulose.

39. The pharmaceutical composition of claim 6 , wherein the expandable polymer comprises hydroxypropylmethylcellulose, the first polymer is a copolymer of ethyl acrylate and methyl methacrylate, and the second polymer is a copolymer of ethyl acrylate and methyl methacrylate.

40. The pharmaceutical composition of claim 6 , wherein the drug is morphine.

41. The pharmaceutical composition of claim 6 , wherein the drug is oxycodone.

42. The pharmaceutical composition of claim 6 , wherein the drug is oxymorphone.

43. The pharmaceutical composition of claim 6 , wherein the drug is hydrocodone.

44. The pharmaceutical composition of claim 6 , wherein the drug is hydromorphone.

45. The pharmaceutical composition of claim 8 , wherein the expandable polymer comprises hydroxypropylmethylcellulose.

46. The pharmaceutical composition of claim 8 , wherein the expandable polymer comprises hydroxypropylmethylcellulose, the first polymer is a copolymer of ethyl acrylate and methyl methacrylate, and the second polymer is a copolymer of ethyl acrylate and methyl methacrylate.

47. The pharmaceutical composition of claim 8 , wherein the drug is morphine.

48. The pharmaceutical composition of claim 8 , wherein the drug is oxycodone.

49. The pharmaceutical composition of claim 8 , wherein the drug is oxymorphone.

50. The pharmaceutical composition of claim 8 , wherein the drug is hydrocodone.

51. The pharmaceutical composition of claim 8 , wherein the drug is hydromorphone.

52. The pharmaceutical composition of claim 9 , wherein the expandable polymer comprises hydroxypropylmethylcellulose.

53. The pharmaceutical composition of claim 9 , wherein the expandable polymer comprises hydroxypropylmethylcellulose, the first polymer is a copolymer of ethyl acrylate and methyl methacrylate, and the second polymer is a copolymer of ethyl acrylate and methyl methacrylate.

54. The pharmaceutical composition of claim 9 , wherein the drug is morphine.

55. The pharmaceutical composition of claim 9 , wherein the drug is oxycodone.

56. The pharmaceutical composition of claim 9 , wherein the drug is oxymorphone.

57. The pharmaceutical composition of claim 9 , wherein the drug is hydrocodone.

58. The pharmaceutical composition of claim 9 , wherein the drug is hydromorphone.

59. An oral, extended release pharmaceutical composition in tablet form configured to deter abuse, comprising:

an inner expansion layer that does not contain any drug and comprises a hydrophilic expandable polymer that forms a gel when exposed to a liquid comprising water and/or alcohol, wherein the expandable polymer is selected from the group consisting of methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, hydroxypropylmethylcellulose, alginic acid, tragacanth, and combinations thereof;

a barrier layer that substantially covers the expansion layer, wherein the barrier layer comprises a first polymer comprising a copolymer of ethyl acrylate and methyl methacrylate, wherein when the pharmaceutical composition is administered in intact form, the first polymer of the barrier layer is substantially undissolved in the gastrointestinal (GI) tract; and

a diffusion layer covering the barrier layer, the diffusion layer comprising a drug comprising an opioid in a pharmaceutically effective amount and a second polymer comprising a copolymer of ethyl acrylate and methyl methacrylate, wherein the drug is substantially homogeneously distributed within the second polymer and diffuses from the diffusion layer within the GI tract,

wherein the diffusion layer is bonded to the barrier layer by curing the layers together, wherein the pharmaceutical composition does not comprise a drug that is not an opioid agonist or a central nervous system stimulant, and wherein the diffusion layer is the only drug-containing layer in the pharmaceutical composition,

wherein the second polymer is present in an amount sufficient to release at least 50% of the amount of drug after 8 hours after administration in intact form, and wherein when the pharmaceutical composition is orally or intranasally administered in crushed form to a subject, the Cmax/AUC achieved 8 hours after administration is lower than the Cmax/AUC achieved 8 hours after administration of a crushed bioequivalent composition not configured to deter abuse.

60. The pharmaceutical composition of claim 59 , wherein the expandable polymer is selected from the group consisting of: methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, and hydroxypropylmethylcellulose.

61. The pharmaceutical composition of claim 59 , wherein the expandable polymer comprises hydroxypropylmethylcellulose.

62. The pharmaceutical composition of claim 59 , wherein the drug is morphine.

63. The pharmaceutical composition of claim 59 , wherein the drug is oxycodone.

64. The pharmaceutical composition of claim 59 , wherein the drug is oxymorphone.

65. The pharmaceutical composition of claim 59 , wherein the drug is hydrocodone.

66. The pharmaceutical composition of claim 59 , wherein the drug is hydromorphone.

67. An oral, extended release pharmaceutical composition in tablet form configured to deter abuse, comprising:

an inner expansion layer that does not contain any drug and comprises a hydrophilic expandable polymer that forms a gel when exposed to a liquid comprising water and/or alcohol, wherein the expandable polymer is selected from the group consisting of methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, hydroxypropylmethylcellulose, alginic acid, tragacanth, and combinations thereof;

a barrier layer that substantially covers the expansion layer, wherein the barrier comprises a first polymer comprising a copolymer of ethyl acrylate and methyl methacrylate, wherein when the pharmaceutical composition is administered in intact form, the first polymer of the barrier layer is substantially undissolved in the gastrointestinal (GI) tract; and

a diffusion layer covering the barrier layer, the diffusion layer comprising a drug comprising an opioid in a pharmaceutically effective amount and a second polymer comprising a copolymer of ethyl acrylate and methyl methacrylate, wherein the drug is substantially homogeneously distributed within the second polymer and diffuses from the diffusion layer within the GI tract,

wherein the diffusion layer is bonded to the barrier layer by curing the layers together, wherein the pharmaceutical composition does not comprise a drug that is not an opioid agonist or a central nervous system stimulant, and wherein the diffusion layer is the only drug-containing layer in the pharmaceutical composition,

wherein the second polymer is present in an amount sufficient to release at least 50% of the amount of drug after 8 hours after administration in intact form,

wherein when the pharmaceutical composition is orally or intranasally administered in crushed form to a subject, the Cmax and/or AUC achieved 8 hours after administration is lower than the Cmax and/or AUC achieved 8 hours after administration of a crushed bioequivalent composition not configured to deter abuse.

68. The pharmaceutical composition of claim 67 , wherein the expandable polymer is selected from the group consisting of: methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, and hydroxypropylmethylcellulose.

69. The pharmaceutical composition of claim 67 , wherein the expandable polymer comprises hydroxypropylmethylcellulose.

70. The pharmaceutical composition of claim 67 , wherein the drug is morphine.

71. The pharmaceutical composition of claim 67 , wherein the drug is oxycodone.

72. The pharmaceutical composition of claim 67 , wherein the drug is oxymorphone.

73. The pharmaceutical composition of claim 67 , wherein the drug is hydrocodone.

74. The pharmaceutical composition of claim 67 , wherein the drug is hydromorphone.

75. An oral, extended release pharmaceutical composition in tablet form configured to deter abuse, comprising:

an inner expansion layer that does not contain any drug and comprises a hydrophilic expandable polymer that forms a gel when exposed to a liquid comprising water and/or alcohol, wherein the expandable polymer is selected from the group consisting of methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, hydroxypropylmethylcellulose, alginic acid, tragacanth, and combinations thereof;

a barrier layer that substantially covers the expansion layer, wherein the barrier layer comprises a first polymer comprising a copolymer of ethyl acrylate and methyl methacrylate, wherein when the pharmaceutical composition is administered in intact form, the first polymer of the barrier layer is substantially undissolved in the gastrointestinal (GI) tract; and

a diffusion layer covering the barrier layer, the diffusion layer comprising a drug comprising an opioid in a pharmaceutically effective amount and a second polymer comprising a copolymer of ethyl acrylate and methyl methacrylate, wherein the drug is substantially homogeneously distributed within the second polymer and diffuses from the diffusion layer within the GI tract,

wherein the diffusion layer is bonded to the barrier layer by curing the layers together, wherein the pharmaceutical composition does not comprise a drug that is not an opioid agonist or a central nervous system stimulant, and wherein the diffusion layer is the only drug-containing layer in the pharmaceutical composition,

wherein the second polymer is present in an amount sufficient to release at least 50% of the amount of drug after 8 hours after administration in intact form, and

wherein when the pharmaceutical composition is orally administered in crushed form to a subject, the rate of drug released from the composition at 4 hours after administration is substantially the same or lower than the rate of drug released at 4 hours after administration when the pharmaceutical composition is administered in intact form.

76. The pharmaceutical composition of claim 75 , wherein the expandable polymer is selected from the group consisting of: methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, and hydroxypropylmethylcellulose.

77. The pharmaceutical composition of claim 75 , wherein the expandable polymer comprises hydroxypropylmethylcellulose.

78. The pharmaceutical composition of claim 75 , wherein the drug is morphine.

79. The pharmaceutical composition of claim 75 , wherein the drug is oxycodone.

80. The pharmaceutical composition of claim 75 , wherein the drug is oxymorphone.

81. The pharmaceutical composition of claim 75 , wherein the drug is hydrocodone.

82. The pharmaceutical composition of claim 75 , wherein the drug is hydromorphone.

83. An oral, extended release pharmaceutical composition in tablet form configured to deter abuse, comprising:

an inner expansion layer that does not contain any drug and comprises a hydrophilic expandable polymer that forms a gel when exposed to a liquid comprising water and/or alcohol, wherein the expandable polymer is selected from the group consisting of methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, hydroxypropylmethylcellulose, alginic acid, tragacanth, and combinations thereof;

a barrier layer that substantially covers the expansion layer, wherein the barrier layer comprises a first polymer comprising a copolymer of ethyl acrylate and methyl methacrylate, wherein when the pharmaceutical composition is administered in intact form, the first polymer of the barrier layer is substantially undissolved in the gastrointestinal (GI) tract; and

a diffusion layer covering the barrier layer, the diffusion layer comprising a drug comprising an opioid in a pharmaceutically effective amount and a second polymer comprising a copolymer of ethyl acrylate and methyl methacrylate, wherein the drug is substantially homogeneously distributed within the second polymer and diffuses from the diffusion layer within the GI tract,

wherein the diffusion layer is bonded to the barrier layer by curing the layers together, wherein the pharmaceutical composition does not comprise a drug that is not an opioid agonist or a central nervous system stimulant, and wherein the diffusion layer is the only drug-containing layer in the pharmaceutical composition,

wherein the second polymer is present in an amount sufficient to release at least 50% of the amount of drug after 8 hours after administration in intact form, and

wherein when the pharmaceutical composition is orally administered in crushed form to a subject, the amount of drug released from the composition 8 hours after administration is substantially the same or lower than the amount of drug released 8 hours after administration of the pharmaceutical composition in intact form.

84. The pharmaceutical composition of claim 83 , wherein the expandable polymer is selected from the group consisting of: methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, and hydroxypropylmethylcellulose.

85. The pharmaceutical composition of claim 83 , wherein the expandable polymer comprises hydroxypropylmethylcellulose.

86. The pharmaceutical composition of claim 83 , wherein the drug is morphine.

87. The pharmaceutical composition of claim 83 , wherein the drug is oxycodone.

88. The pharmaceutical composition of claim 83 , wherein the drug is oxymorphone.

89. The pharmaceutical composition of claim 83 , wherein the drug is hydrocodone.

90. The pharmaceutical composition of claim 83 , wherein the drug is hydromorphone.

91. The pharmaceutical composition of claim 83 , wherein when the pharmaceutical composition is administered in crushed form to a subject, the amount of drug released from the composition at 8 hours after administration is no more than 75% of the amount of drug released at 8 hours after administration of the pharmaceutical composition in intact form.

92. An oral, extended release pharmaceutical composition in tablet form configured to deter abuse, comprising:

an inner expansion layer that does not contain any drug and comprises a hydrophilic expandable polymer that forms a gel when exposed to a liquid comprising water and/or alcohol, wherein the expandable polymer is selected from the group consisting of methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, hydroxypropylmethylcellulose, alginic acid, tragacanth, and combinations thereof;

a barrier layer that substantially covers the expansion layer, wherein the barrier layer comprises a first polymer comprising a copolymer of ethyl acrylate and methyl methacrylate, wherein when the pharmaceutical composition is administered in intact form, the first polymer of the barrier layer is substantially undissolved in the gastrointestinal (GI) tract; and

a diffusion layer covering the barrier layer, the diffusion layer comprising a drug comprising an opioid in a pharmaceutically effective amount and a second polymer comprising a copolymer of ethyl acrylate and methyl methacrylate, wherein the drug is substantially homogeneously distributed within the second polymer and diffuses from the diffusion layer within the GI tract,

wherein the diffusion layer is bonded to the barrier layer by curing the layers together, wherein the pharmaceutical composition does not comprise a drug that is not an opioid agonist or a central nervous system stimulant, and wherein the diffusion layer is the only drug-containing layer in the pharmaceutical composition,

wherein the second polymer is present in an amount sufficient to release at least 50% of the amount of drug after 8 hours after administration in intact form, and

wherein when the pharmaceutical composition is orally administered in intact form, at least 50% of the amount of drug is released 8 hours after administration and when the pharmaceutical composition is administered in crushed form no more than 40% of the amount of drug is released 1 hour after administration.

93. The pharmaceutical composition of claim 92 , wherein the expandable polymer is selected from the group consisting of: methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, and hydroxypropylmethylcellulose.

94. The pharmaceutical composition of claim 92 , wherein the expandable polymer comprises hydroxypropylmethylcellulose.

95. The pharmaceutical composition of claim 92 , wherein the drug is morphine.

96. The pharmaceutical composition of claim 92 , wherein the drug is oxycodone.

97. The pharmaceutical composition of claim 92 , wherein the drug is oxymorphone.

98. The pharmaceutical composition of claim 92 , wherein the drug is hydrocodone.

99. The pharmaceutical composition of claim 92 , wherein the drug is hydromorphone.

100. The pharmaceutical composition of claim 92 , wherein when the pharmaceutical composition is administered in crushed form to a subject no more than 35% of the amount of drug is released 15 minutes after administration.

101. An oral, immediate release pharmaceutical composition in tablet form configured to deter abuse, comprising:

an inner expansion layer that does not contain any drug and comprises a hydrophilic expandable polymer that forms a gel when exposed to a liquid comprising water and/or alcohol, wherein the expandable polymer is selected from the group consisting of methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, hydroxypropylmethylcellulose, alginic acid, tragacanth, and combinations thereof;

a barrier layer that substantially covers the expansion layer, wherein the barrier layer comprises a first polymer comprising a copolymer of ethyl acrylate and methyl methacrylate, wherein when the pharmaceutical composition is administered in intact form, the first polymer of the barrier layer is substantially undissolved in the gastrointestinal (GI) tract; and

a diffusion layer covering the barrier layer, the diffusion layer comprising a drug comprising an opioid in a pharmaceutically effective amount, wherein the drug is substantially homogeneously distributed within the second polymer and diffuses from the diffusion layer within the GI tract,

wherein the diffusion layer is bonded to the barrier layer by curing the layers together, wherein the pharmaceutical composition does not comprise a drug that is not an opioid agonist or a central nervous system stimulant, and wherein the diffusion layer is the only drug-containing layer in the pharmaceutical composition,

wherein the second polymer is present in an amount sufficient to release at least 90% of the amount of drug in 1 hour after administration in intact form, and

wherein when the pharmaceutical composition is orally administered in intact form, at least 90% of the amount of drug is released in 1 hour after administration, and when the pharmaceutical composition is orally administered in crushed form, no more than 75% of the amount of drug is released in 1 hour after administration.

102. The pharmaceutical composition of claim 101 , wherein the expandable polymer is selected from the group consisting of: methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, and hydroxypropylmethylcellulose.

103. The pharmaceutical composition of claim 101 , wherein the expandable polymer comprises hydroxypropylmethylcellulose.

104. The pharmaceutical composition of claim 101 , wherein the drug is morphine.

105. The pharmaceutical composition of claim 101 , wherein the drug is oxycodone.

106. The pharmaceutical composition of claim 101 , wherein the drug is oxymorphone.

107. The pharmaceutical composition of claim 101 , wherein the drug is hydrocodone.

108. The pharmaceutical composition of claim 101 , wherein the drug is hydromorphone.

109. An oral, extended release pharmaceutical composition in tablet form configured to deter abuse, comprising:

an inner expansion layer that does not contain any drug and comprises a hydrophilic expandable polymer that forms a gel when exposed to a liquid comprising water and/or alcohol, wherein the expandable polymer is selected from the group consisting of methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, hydroxypropylmethylcellulose, alginic acid, tragacanth, and combinations thereof;

a barrier layer that substantially covers the expansion layer, wherein the barrier layer comprises a first polymer comprising a copolymer of ethyl acrylate and methyl methacrylate, wherein when the pharmaceutical composition is administered in intact form, the first polymer of the barrier layer is substantially undissolved in the gastrointestinal (GI) tract; and

a diffusion layer covering the barrier layer, the diffusion layer comprising a drug comprising an opioid in a pharmaceutically effective amount and a second polymer comprising a copolymer of ethyl acrylate and methyl methacrylate, wherein the drug is substantially homogeneously distributed within the second polymer and diffuses from the diffusion layer within the GI tract,

wherein the diffusion layer is bonded to the barrier layer by curing the layers together, wherein the pharmaceutical composition does not comprise a drug that is not an opioid agonist, zaleplon, or a central nervous system stimulant, and wherein the diffusion layer is the only drug-containing layer in the pharmaceutical composition,

wherein the second polymer is present in an amount sufficient to release at least 50% of the amount of drug after 8 hours after administration in intact form, and

wherein when the pharmaceutical composition is administered in intact form, at least 50% of the amount of drug is released after 8 hours after administration, and wherein when the pharmaceutical composition is administered in crushed form to a subject, no more than 40% of the amount of drug is released in 1 hour after administration, and the intensity of euphoria is lower than the intensity of euphoria achieved after administration of a crushed bioequivalent composition not comprising a barrier layer comprising a first polymer and a diffusion layer comprising drug and a second polymer.

110. The pharmaceutical composition of claim 109 , wherein the expandable polymer is selected from the group consisting of: methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, and hydroxypropylmethylcellulose.

111. The pharmaceutical composition of claim 109 , wherein the expandable polymer comprises hydroxypropylmethylcellulose.

112. The pharmaceutical composition of claim 109 , wherein the drug is morphine.

113. The pharmaceutical composition of claim 109 , wherein the drug is oxycodone.

114. The pharmaceutical composition of claim 109 , wherein the drug is oxymorphone.

115. The pharmaceutical composition of claim 109 , wherein the drug is hydrocodone.

116. The pharmaceutical composition of claim 109 , wherein the drug is hydromorphone.