Abuse resistant oral opioid formulations

1. An oral, extended release abuse deterrent pharmaceutical composition, in the form of a layered tablet configured to deter abuse, comprising:

an expansion layer comprising an 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 substantially covering the expansion layer, wherein the barrier layer comprises a first polymer selected from the group consisting of: acrylic or methacrylic polymers or copolymers thereof, and 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, wherein the diffusion layer comprises a drug and a second polymer selected from the group consisting of: acrylic or methacrylic polymers or copolymers thereof,

wherein the drug comprises an opioid agonist,

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

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 the only drug-containing layer in the pharmaceutical composition,

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

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 crushed to produce particles having a particle size from 500 mesh to 8 mesh, the relative surface area of the diffusion layer increases by no more than 50%.

2. The oral pharmaceutical composition of claim 1 , wherein the diffusion layer comprises a pore forming agent.

3. The oral pharmaceutical composition of claim 1 , wherein the thickness of the expansion layer is about 5 to 95% of the thickness of the tablet, and wherein when the pharmaceutical composition is crushed and particles of the pharmaceutical composition comprising the expansion layer are formed and exposed to a liquid, the expansion polymer of the expansion layer absorbs at least a portion of the liquid.

4. The oral pharmaceutical composition of claim 1 , wherein the first polymer and the second polymer are a copolymer of ethyl acrylate and methyl methacrylate, and wherein when the pharmaceutical composition is 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 when the pharmaceutical composition is administered to a subject in intact form.

5. The oral pharmaceutical composition of claim 1 , wherein the first polymer and the second polymer are a copolymer of ethyl acrylate and methyl methacrylate, and wherein when the pharmaceutical composition is administered in crushed form to a subject, the Cmax and/or AUC achieved 8 hours after administration is 20-75% lower than the Cmax and/or AUC achieved 8 hours after administration when the pharmaceutical composition is administered to a subject in intact form.

6. The oral pharmaceutical composition of claim 1 , wherein the first polymer and the second polymer are a copolymer of ethyl acrylate and methyl methacrylate, and wherein when the pharmaceutical composition is 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.

7. The oral pharmaceutical composition of claim 1 , wherein the first polymer and the second polymer are a copolymer of ethyl acrylate and methyl methacrylate, and wherein when the pharmaceutical composition is 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.

8. The oral pharmaceutical composition of claim 1 , wherein the first polymer and the second polymer are a copolymer of ethyl acrylate and methyl methacrylate, and wherein when the pharmaceutical composition is 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.

9. The oral pharmaceutical composition of claim 1 , wherein the first polymer and the second polymer are a copolymer of ethyl acrylate and methyl methacrylate, and wherein when the pharmaceutical composition is 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 when the pharmaceutical composition is administered in intact form.

10. The oral pharmaceutical composition of claim 1 , wherein the first polymer and the second polymer are a copolymer of ethyl acrylate and methyl methacrylate, and wherein when the pharmaceutical composition is administered in crushed form to a subject, the amount of drug released from the composition 8 hours after administration is no more than 75% of the amount of drug released 8 hours after administration when the pharmaceutical composition is administered in intact form.

11. The oral pharmaceutical composition of claim 1 , wherein the first polymer and the second polymer are a copolymer of ethyl acrylate and methyl methacrylate, 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 within 1 hour after administration.

12. The oral pharmaceutical composition of claim 1 , wherein the first polymer and the second polymer are a copolymer of ethyl acrylate and methyl methacrylate, and wherein when the pharmaceutical composition is administered in crushed form to a subject, no more than 35% of the amount of drug is released within 15 minutes after administration.

13. The oral pharmaceutical composition of claim 1 , wherein the drug is an opioid agonist selected from the group consisting of alfentanil, allylprodine, alphaprodine, anileridine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, desomorphine, dextromoramide, dezocine, diampromide, diamorphone, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene, hydrocodone, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levorphanol, levophenacylmorphan, lofentanil, meperidine, meptazinol, metazocine, methadone, metopon, morphine, myrophine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, nalbuphene, normorphine, norpipanone, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, propoxyphene, sufentanil, tilidine, tramadol, and pharmaceutically acceptable salts thereof.

14. The oral pharmaceutical composition of claim 1 , wherein the opioid agonist is selected from the group consisting of: oxycodone or a pharmaceutically acceptable salt thereof, which is present in an amount of about 5 mg to about 400 mg; morphine or a pharmaceutically acceptable salt thereof, which is present in an amount of about 15 mg to about 800 mg; hydromorphone or a pharmaceutically acceptable salt thereof, which is present in an amount of about 1 mg to about 64 mg; hydrocodone or a pharmaceutically acceptable salt thereof, which is present in an amount of about 5 mg to about 400 mg; and oxymorphone or a pharmaceutically acceptable salt thereof, which is present in an amount of about 4 mg to about 80 mg.

15. The oral pharmaceutical composition of claim 1 , wherein the barrier layer and diffusion layer are physically bonded, and wherein when the pharmaceutical composition is administered in crushed form to a subject, the intensity of euphoria is lower than the intensity of euphoria achieved after administration of a crushed bioequivalent composition not configured to deter abuse.

16. The oral pharmaceutical composition of claim 1 , wherein the expansion polymer is present in the range of 5 to 90% by weight based on the total weight of the tablet.

17. The oral pharmaceutical composition of claim 1 , wherein the second polymer of the diffusion layer provides a timed release of drug over a period of about 6 to about 24 hours.

18. The oral pharmaceutical composition of claim 1 , wherein the drug comprises morphine or a pharmaceutically acceptable salt thereof.

19. The oral pharmaceutical composition of claim 1 , wherein the drug comprises oxycodone or a pharmaceutically acceptable salt thereof.

20. The oral pharmaceutical composition of claim 1 , wherein the drug comprises oxymorphone or a pharmaceutically acceptable salt thereof.

21. The oral pharmaceutical composition of claim 1 , wherein the drug comprises hydrocodone or a pharmaceutically acceptable salt thereof.

22. The oral pharmaceutical composition of claim 1 , wherein the drug comprises hydromorphone or a pharmaceutically acceptable salt thereof.

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

24. The pharmaceutical composition of claim 1 , wherein the expandable polymer is selected from the group consisting of: methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, and hydroxypropylmethylcellulose.

25. The pharmaceutical composition of claim 1 , wherein 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 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.

27. An oral, extended release abuse deterrent pharmaceutical composition, in the form of a layered tablet configured to deter abuse, comprising:

an expansion layer comprising an 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 substantially covering the expansion layer wherein the barrier layer comprises a first polymer, wherein the first polymer is a copolymer of ethyl acrylate and methyl methacrylate, and 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, wherein the diffusion layer comprises a drug and a second polymer, wherein the second polymer is a copolymer of ethyl acrylate and methyl methacrylate and wherein the drug comprises an opioid agonist,

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

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 the only drug-containing layer in the pharmaceutical composition,

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

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 crushed to produce particles having a particle size from 500 mesh to 8 mesh, the relative surface area of the diffusion layer increases by no more than 50%.

28. The oral pharmaceutical composition of claim 27 , wherein the diffusion layer comprises a pore forming agent.

29. The oral pharmaceutical composition of claim 27 , wherein the expandable polymer is selected from the group consisting of: methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, and hydroxypropylmethylcellulose.

30. The oral pharmaceutical composition of claim 27 , wherein the expandable polymer comprises hydroxypropylmethylcellulose.

31. The oral pharmaceutical composition of claim 27 , wherein the expandable polymer comprises hydroxypropylmethylcellulose, and the drug comprises morphine or a pharmaceutically acceptable salt thereof.

32. The oral pharmaceutical composition of claim 1 , wherein the expandable polymer comprises hydroxypropylmethylcellulose, the first polymer and second polymer are a copolymer of ethyl acrylate and methyl methacrylate, and the drug comprises morphine or a pharmaceutically acceptable salt thereof in an amount of about 15 mg to about 800 mg.

33. The oral pharmaceutical composition of claim 27 , wherein the thickness of the expansion layer is about 5 to 95% of the thickness of the tablet, and wherein when the pharmaceutical composition is crushed and particles of the pharmaceutical composition comprising the expansion layer are formed and exposed to a liquid, the expansion polymer of the expansion layer absorbs at least a portion of the liquid.

34. The oral pharmaceutical composition of claim 27 , wherein when the pharmaceutical composition is 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 when the pharmaceutical composition is administered to a subject in intact form.

35. The oral pharmaceutical composition of claim 27 , wherein when the pharmaceutical composition is administered in crushed form to a subject, the Cmax and/or AUC achieved 8 hours after administration is 20-75% lower than the Cmax and/or AUC achieved 8 hours after administration when the pharmaceutical composition is administered to a subject in intact form.

36. The oral pharmaceutical composition of claim 27 , wherein when the pharmaceutical composition is 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.

37. The oral pharmaceutical composition of claim 27 , wherein when the pharmaceutical composition is 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.

38. The oral pharmaceutical composition of claim 27 , wherein when the pharmaceutical composition is 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.

39. The oral pharmaceutical composition of claim 27 , wherein when the pharmaceutical composition is 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 when the pharmaceutical composition is administered in intact form.

40. The oral pharmaceutical composition of claim 27 , wherein when the pharmaceutical composition is administered in crushed form to a subject, the amount of drug released from the composition 8 hours after administration is no more than 75% of the amount of drug released 8 hours after administration when the pharmaceutical composition is administered in intact form.

41. The oral pharmaceutical composition of claim 27 , wherein when the pharmaceutical composition is administered in crushed form or no more than 40% of the amount of drug is released within 1 hour after administration.

42. The oral pharmaceutical composition of claim 27 , wherein when the pharmaceutical composition is administered in crushed form no more than 35% of the amount of drug is released within 15 minutes after administration.

43. The oral pharmaceutical composition of claim 27 , wherein the barrier layer and diffusion layer are physically bonded, and wherein when the pharmaceutical composition is administered in crushed form to a subject, the intensity of euphoria is lower than the intensity of euphoria achieved after administration of a crushed bioequivalent composition not configured to deter abuse.

44. The oral pharmaceutical composition of claim 27 , wherein the second polymer of the diffusion layer provides a timed release of drug over a period of about 6 to about 24 hours.

45. The oral pharmaceutical composition of claim 27 , wherein the drug comprises morphine or a pharmaceutically acceptable salt thereof.

46. The oral pharmaceutical composition of claim 27 , wherein the drug comprises oxycodone or a pharmaceutically acceptable salt thereof.

47. The oral pharmaceutical composition of claim 27 , wherein the drug comprises oxymorphone or a pharmaceutically acceptable salt thereof.

48. The oral pharmaceutical composition of claim 27 , wherein the drug comprises hydrocodone or a pharmaceutically acceptable salt thereof.

49. The oral pharmaceutical composition of claim 27 , wherein the drug comprises hydromorphone or a pharmaceutically acceptable salt thereof.

50. The oral pharmaceutical composition of claim 27 , wherein the opioid agonist is selected from the group consisting of: oxycodone or a pharmaceutically acceptable salt thereof, which is present in an amount of about 5 mg to about 400 mg; morphine or a pharmaceutically acceptable salt thereof, which is present in an amount of about 15 mg to about 800 mg; hydromorphone or a pharmaceutically acceptable salt thereof, which is present in an amount of about 1 mg to about 64 mg; hydrocodone or a pharmaceutically acceptable salt thereof, which is present in an amount of about 5 mg to about 400 mg; and oxymorphone or a pharmaceutically acceptable salt thereof, which is present in an amount of about 4 mg to about 80 mg.

51. An oral, immediate release abuse deterrent pharmaceutical composition, in the form of a layered tablet configured to deter abuse, comprising:

an expansion layer comprising an 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 substantially covering the expansion layer, wherein the barrier layer comprises a first polymer selected from the group consisting of: acrylic or methacrylic polymers or copolymers thereof, and 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 wherein the diffusion layer comprises a drug and a second polymer selected from the group consisting of: acrylic or methacrylic polymers or copolymers thereof,

wherein the drug comprises an opioid agonist,

wherein the diffusion layer is bonded to the barrier layer by a process comprising heat such that the layers are not separable,

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 the only drug-containing layer in the pharmaceutical composition,

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

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, and

wherein when the pharmaceutical composition is crushed to produce particles having a particle size from 500 mesh to 8 mesh, the relative surface area of the diffusion layer increases by no more than 50%.

52. The oral pharmaceutical composition of claim 51 , wherein the diffusion layer comprises a pore forming agent.

53. The oral pharmaceutical composition of claim 51 , wherein the thickness of the expansion layer is about 5 to 95% of the thickness of the tablet, and wherein when the pharmaceutical composition is crushed and particles of the pharmaceutical composition comprising the expansion layer are formed and exposed to a liquid, the expansion polymer of the expansion layer absorbs at least a portion of the liquid.

54. The oral pharmaceutical composition of claim 51 , wherein the first polymer and the second polymer are a copolymer of ethyl acrylate and methyl methacrylate, and wherein when the pharmaceutical composition is 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 when the pharmaceutical composition is administered to a subject in intact form.

55. The oral pharmaceutical composition of claim 51 , wherein the first polymer and the second polymer are a copolymer of ethyl acrylate and methyl methacrylate, and wherein when the pharmaceutical composition is administered in crushed form to a subject, the Cmax and/or AUC achieved 8 hours after administration is 20-75% lower than the Cmax and/or AUC achieved 8 hours after administration when the pharmaceutical composition is administered to a subject in intact form.

56. The oral pharmaceutical composition of claim 51 , wherein the first polymer and the second polymer are a copolymer of ethyl acrylate and methyl methacrylate, and wherein when the pharmaceutical composition is 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.

57. The oral pharmaceutical composition of claim 51 , wherein the first polymer and the second polymer are a copolymer of ethyl acrylate and methyl methacrylate, and wherein when the pharmaceutical composition is 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.

58. The oral pharmaceutical composition of claim 51 , wherein the first polymer and the second polymer are a copolymer of ethyl acrylate and methyl methacrylate, and wherein when the pharmaceutical composition is 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.

59. The oral pharmaceutical composition of claim 51 , wherein the first polymer and the second polymer are a copolymer of ethyl acrylate and methyl methacrylate, and wherein when the pharmaceutical composition is 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 when the pharmaceutical composition is administered in intact form.

60. The oral pharmaceutical composition of claim 51 , wherein the first polymer and the second polymer are a copolymer of ethyl acrylate and methyl methacrylate, and wherein when the pharmaceutical composition is administered in crushed form to a subject, the amount of drug released from the composition 8 hours after administration is no more than 75% of the amount of drug released 8 hours after administration when the pharmaceutical composition is administered in intact form.

61. The oral pharmaceutical composition of claim 51 , wherein the first polymer and the second polymer are a copolymer of ethyl acrylate and methyl methacrylate, and wherein when the pharmaceutical composition is administered in crushed form, no more than 75% of the amount of drug is released within 1 hour after administration.

62. The oral pharmaceutical composition of claim 51 , wherein the first polymer and the second polymer are a copolymer of ethyl acrylate and methyl methacrylate, and wherein when the pharmaceutical composition is administered in crushed form no more than 35% of the amount of drug is released within 15 minutes after administration.

63. The oral pharmaceutical composition of claim 51 , wherein the barrier layer and diffusion layer are physically bonded, and wherein when the pharmaceutical composition is administered in crushed form to a subject, the intensity of euphoria is lower than the intensity of euphoria achieved after administration of a crushed bioequivalent composition not configured to deter abuse.

64. The oral pharmaceutical composition of claim 51 , wherein the drug comprises morphine or a pharmaceutically acceptable salt thereof.

65. The oral pharmaceutical composition of claim 51 , wherein the drug comprises oxycodone or a pharmaceutically acceptable salt thereof.

66. The oral pharmaceutical composition of claim 51 , wherein the drug comprises oxymorphone or a pharmaceutically acceptable salt thereof.

67. The oral pharmaceutical composition of claim 51 , wherein the drug comprises hydrocodone or a pharmaceutically acceptable salt thereof.

68. The oral pharmaceutical composition of claim 51 , wherein the drug comprises hydromorphone or a pharmaceutically acceptable salt thereof.

69. The oral pharmaceutical composition of claim 51 , wherein the opioid agonist is selected from the group consisting of: oxycodone or a pharmaceutically acceptable salt thereof, which is present in an amount of about 5 mg to about 400 mg; morphine or a pharmaceutically acceptable salt thereof, which is present in an amount of about 15 mg to about 800 mg; hydromorphone or a pharmaceutically acceptable salt thereof, which is present in an amount of about 1 mg to about 64 mg; hydrocodone or a pharmaceutically acceptable salt thereof, which is present in an amount of about 5 mg to about 400 mg; and oxymorphone or a pharmaceutically acceptable salt thereof, which is present in an amount of about 4 mg to about 80 mg.

70. The pharmaceutical composition of claim 51 , wherein 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.

71. The oral pharmaceutical composition of claim 51 , wherein the expandable polymer comprises hydroxypropylmethylcellulose.

72. The pharmaceutical composition of claim 51 , wherein the expandable polymer is selected from the group consisting of: methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, and hydroxypropylmethylcellulose.

73. The pharmaceutical composition of claim 51 , 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.

74. An oral, immediate release abuse deterrent pharmaceutical composition, in the form of a layered tablet configured to deter abuse, comprising:

an expansion layer comprising an 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 substantially covering the expansion layer, wherein the barrier layer comprises a first polymer, wherein the first polymer is a copolymer of ethyl acrylate and methyl methacrylate, and 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 wherein the diffusion layer comprises a drug and a second polymer, wherein the second polymer is a copolymer of ethyl acrylate and methyl methacrylate and wherein the drug comprises an opioid agonist,

wherein the diffusion layer is bonded to the barrier layer by a process comprising heat such that the layers are not separable,

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 the only drug-containing layer in the pharmaceutical composition,

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

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, and

wherein when the pharmaceutical composition is crushed to produce particles having a particle size from 500 mesh to 8 mesh, the relative surface area of the diffusion layer increases by no more than 50%.

75. The oral pharmaceutical composition of claim 74 , wherein the diffusion layer comprises a pore forming agent.

76. The oral pharmaceutical composition of claim 74 , wherein the thickness of the expansion layer is about 5 to 95% of the thickness of the tablet, and wherein when the pharmaceutical composition is crushed and particles of the pharmaceutical composition comprising the expansion layer are formed and exposed to a liquid, the expansion polymer of the expansion layer absorbs at least a portion of the liquid.

77. The oral pharmaceutical composition of claim 74 , wherein when the pharmaceutical composition is 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 when the pharmaceutical composition is administered to a subject in intact form.

78. The oral pharmaceutical composition of claim 74 , wherein when the pharmaceutical composition is administered in crushed form, the Cmax and/or AUC achieved 8 hours after administration is 20-75% lower than the Cmax and/or AUC achieved 8 hours after administration when the pharmaceutical composition is administered to a subject in intact form.

79. The oral pharmaceutical composition of claim 74 , wherein when the pharmaceutical composition is 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.

80. The oral pharmaceutical composition of claim 74 , wherein when the pharmaceutical composition is 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.

81. The oral pharmaceutical composition of claim 74 , wherein when the pharmaceutical composition is 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.

82. The oral pharmaceutical composition of claim 74 , wherein when the pharmaceutical composition is 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 when the pharmaceutical composition is administered in intact form.

83. The oral pharmaceutical composition of claim 74 , wherein when the pharmaceutical composition is administered in crushed form to a subject, the amount of drug released from the composition 8 hours after administration is no more than 75% of the amount of drug released 8 hours after administration when the pharmaceutical composition is administered in intact form.

84. The oral pharmaceutical composition of claim 74 , wherein when the pharmaceutical composition is administered in crushed form no more than 75% of the amount of drug is released within 1 hour after administration.

85. The oral pharmaceutical composition of claim 74 , wherein when the pharmaceutical composition is administered in crushed form no more than 35% of the amount of drug is released within 15 minutes after administration.

86. The oral pharmaceutical composition of claim 74 , wherein the barrier layer and diffusion layer are physically bonded, and wherein when the pharmaceutical composition is administered in crushed form to a subject, the intensity of euphoria is lower than the intensity of euphoria achieved after administration of a crushed bioequivalent composition not configured to deter abuse.

87. The oral pharmaceutical composition of claim 74 , wherein the drug comprises morphine or a pharmaceutically acceptable salt thereof.

88. The oral pharmaceutical composition of claim 74 , wherein the drug comprises oxycodone or a pharmaceutically acceptable salt thereof.

89. The oral pharmaceutical composition of claim 74 , wherein the drug comprises oxymorphone or a pharmaceutically acceptable salt thereof.

90. The oral pharmaceutical composition of claim 74 , wherein the drug comprises hydrocodone or a pharmaceutically acceptable salt thereof.

91. The oral pharmaceutical composition of claim 74 , wherein the drug comprises hydromorphone or a pharmaceutically acceptable salt thereof.

92. The oral pharmaceutical composition of claim 74 , wherein the opioid agonist is selected from the group consisting of: oxycodone or a pharmaceutically acceptable salt thereof, which is present in an amount of about 5 mg to about 400 mg; morphine or a pharmaceutically acceptable salt thereof, which is present in an amount of about 15 mg to about 800 mg; hydromorphone or a pharmaceutically acceptable salt thereof, which is present in an amount of about 1 mg to about 64 mg; hydrocodone or a pharmaceutically acceptable salt thereof, which is present in an amount of about 5 mg to about 400 mg; and oxymorphone or a pharmaceutically acceptable salt thereof, which is present in an amount of about 4 mg to about 80 mg.

93. The oral pharmaceutical composition of claim 74 , wherein the expandable polymer comprises hydroxypropylmethylcellulose.

94. The pharmaceutical composition of claim 74 , wherein the expandable polymer is selected from the group consisting of: methylcellulose, sodium carboxymethylcellulose, methylhydroxyethylcellulose, and hydroxypropylmethylcellulose.

95. The pharmaceutical composition of claim 74 , wherein the expandable polymer comprises hydroxypropylmethylcellulose, and the drug comprises morphine or a pharmaceutically acceptable salt thereof in an amount of about 15 mg to about 800 mg.