Pharmaceutical compositions configured to deter dosage form splitting

1. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of: polyacrylates or copolymers thereof, and mixtures thereof; and a diffusion layer substantially covering the barrier layer and comprising a drug and a diffusion polymer selected from the group consisting of: quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers, and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer has a thickness of about 0.1 to 1.0 mm, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

wherein when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the Cmax and/or AUC achieved at 4 hours after administration is substantially the same or lower than the Cmax and/or AUC achieved at 4 hours after administration of a comparable composition in an intact dosage form of equal drug dosage of the administered at least one piece,

and wherein the drug is an opioid.

2. The pharmaceutical composition of claim 1 , wherein the Cmax and/or AUC achieved after 8 hours after administration is at least about 20% lower than the Cmax and/or AUC achieved at 4 hours after administration of a comparable composition in an intact dosage form of equal drug dosage of the administered at least one piece.

3. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of: polyacrylates or copolymers thereof and mixtures thereof; and a diffusion layer substantially covering the barrier layer and comprising a drug and a diffusion polymer selected from the group consisting of: quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers, and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer has a thickness of about 0.1 to 1.0 mm, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

wherein when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the rate of drug released from the dosage form at 4 hours after administration is substantially the same as the rate of drug released at 4 hours after administration from a comparable composition in an intact dosage form of equal drug dosage of the administered at least one piece,

and wherein the drug is an opioid.

4. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of: polyacrylates or copolymers thereof and mixtures thereof; and a diffusion layer substantially covering the barrier layer and comprising a drug and a diffusion polymer selected from the group consisting of: quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer has a thickness of about 0.1 to 1.0 mm, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

wherein when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the Tmax achieved after administration is substantially the same or greater than the Tmax achieved after administration of a comparable composition in an intact dosage form of equal drug dosage of the administered at least one piece,

and the drug is an opioid.

5. The pharmaceutical composition of claim 4 , wherein the Tmax achieved after administration is at least about 20% greater than the Tmax achieved after administration of comparable composition in an intact dosage form of equal drug dosage of the administered at least one piece.

6. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of: polyacrylates or copolymers thereof and mixtures thereof; and a diffusion layer substantially covering the barrier layer and comprising a drug and a diffusion polymer selected from the group consisting of: quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer has a thickness of about 0.1 to 1.0 mm, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

wherein when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the Cmax and/or AUC achieved at 4 hours after administration is substantially the same or lower than the Cmax and/or AUC achieved at 4 hours after administration of an intact dosage form of a bioequivalent drug composition, wherein the drug dosage in the intact dosage form of the bioequivalent drug composition is equal to the drug dosage of the administered at least one piece, and wherein the drug is an opioid.

7. The pharmaceutical composition of claim 6 , wherein the Cmax and/or AUC achieved at 4 hours after administration, is at least about 20% lower than the Cmax and/or AUC achieved after administration of the intact dosage form of the bioequivalent drug composition.

8. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of: polyacrylates or copolymers thereof and mixtures thereof; and a diffusion layer substantially covering the barrier layer and comprising a drug and a diffusion polymer selected from the group consisting of; quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer has a thickness of about 0.1 to 1.0 mm, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

wherein when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the rate of drug released from the dosage form at 4 hours after administration is substantially the same or lower than the rate of drug released from an intact dosage form of a bioequivalent drug composition at 4 hours after administration, wherein the drug dosage in the intact dosage form of the bioequivalent drug composition is equal to the drug dosage of the administered at least one piece,

and wherein the drug is an opioid.

9. The pharmaceutical composition of claim 8 , wherein the rate of drug released from the composition at 4 hours after administration is at least about 20% lower than the rate of drug released from the intact dosage form of the bioequivalent drug composition.

10. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of: polyacrylates or copolymers thereof and mixtures thereof; and a diffusion layer substantially covering the barrier layer and comprising a drug and a diffusion polymer selected from the group consisting of: quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer has a thickness of about 0.1 to 1.0 mm, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

wherein when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the Tmax achieved after administration is substantially the same or greater than the Tmax achieved administration of an intact dosage form of a bioequivalent drug composition, wherein the drug dosage in the intact dosage form of the bioequivalent drug composition is equal to the drug dosage of the administered at least one piece,

and wherein the drug is an opioid.

11. The pharmaceutical composition of claim 10 , wherein the Tmax achieved after administration is at least about 20% greater than the Tmax achieved after administration of the intact dosage form of the bioequivalent drug composition.

12. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of: polyacrylates or copolymers thereof and mixtures thereof; and a diffusion layer substantially covering the barrier layer and comprising a drug and a diffusion polymer selected from the group consisting of: qua ternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer has a thickness of about 0.1 to 1.0 mm, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

wherein when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the Cmax and/or AUC achieved at 4 hours after administration is substantially the same or lower than the Cmax and/or AUC achieved at 4 hours after administration of a divided piece of a bioequivalent drug composition, wherein the divided piece of the bioequivalent drug composition comprises a drug dosage equal to the drug dosage of the administered at least one piece,

and wherein the drug is an opioid.

13. The pharmaceutical composition of claim 12 , wherein the Cmax and/or AUC achieved at 4 hours after administration, is at least about 20% lower than the Cmax and/or AUC achieved at 4 hours after administration of a divided piece of a bioequivalent drug composition, wherein the divided piece of the bioequivalent drug composition comprises a drug dosage equal to the drug dosage of the administered at least one piece.

14. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of: polyacrylates or copolymers thereof and mixtures thereof; and a diffusion layer substantially covering the barrier layer and comprising a drug and a diffusion polymer selected from the group consisting of; quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer has a thickness of about 0.1 to 1.0 mm, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

wherein when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the rate of drug released from the dosage form at 4 hours after administration is substantially the same or lower than the rate of drug released at 4 hours after administration from a divided piece of a bioequivalent drug composition, wherein the divided piece of the bioequivalent drug composition comprises a drug dosage equal to the drug dosage of the administered at least one piece,

and wherein the drug is an opioid.

15. The pharmaceutical composition of claim 14 , wherein the rate of drug released from the composition at 4 hours after administration is at least about 20% lower than the rate of drug released at 4 hours after administration from a divided piece of a bioequivalent drug composition, wherein the divided piece of the bioequivalent drug composition comprises a drug dosage equal to the drug dosage of the administered at least one piece.

16. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of: polyacrylates or copolymers thereof and mixtures thereof; and a diffusion layer substantially covering the barrier layer and comprising a drug and a diffusion polymer selected from the group consisting of: quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer has a thickness of about 0.1 to 1.0 mm, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

wherein when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the Tmax achieved after administration is substantially the same or greater than the Tmax achieved after administration of a divided piece of a bioequivalent drug composition, wherein the divided piece of the bioequivalent drug composition comprises a drug dosage equal to the drug dosage of the administered at least one piece,

and wherein the drug is an opioid.

17. The pharmaceutical composition of claim 16 , wherein the Tmax achieved after administration is at least about 20% greater than the Tmax achieved after administration of a divided piece of a bioequivalent drug composition, wherein the divided piece of the bioequivalent drug composition comprises a drug dosage equal to the drug dosage of the administered at least one piece.

18. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of: polyacrylates or copolymers thereof and mixtures thereof; and a diffusion layer substantially covering the barrier layer and comprising a drug and a diffusion polymer selected from the group consisting of: quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers, and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer has a thickness of about 0.1 to 1.0 mm, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

wherein when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the rate of drug released from the dosage form at 4 hours after administration is at least about 10% lower than the rate of drug released at 4 hours after administration from a comparable composition in an intact dosage form of equal drug dosage of the administered at least one piece,

and wherein the drug is an opioid.

19. The pharmaceutical composition of claim 18 , wherein the rate of drug released from the composition at 4 hours after administration is at least about 20% lower than the rate of drug released at 4 hours after administration from a comparable composition in an intact dosage form of equal drug dosage of the administered at least one piece.

20. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of: polyacrylates or copolymers thereof and mixtures thereof; and a diffusion layer substantially covering the barrier layer and comprising a drug and a diffusion polymer selected from the group consisting of: quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers, and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer comprises about 1 to 30% of the total thickness of the composition, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

wherein when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the Cmax and/or AUC achieved at 4 hours after administration is substantially the same or lower than the Cmax and/or AUC achieved at 4 hours after administration of a comparable composition in an intact dosage form of equal drug dosage of the administered at least one piece,

and wherein the drug is an opioid.

21. The pharmaceutical composition of claim 20 , wherein the Cmax and/or AUC achieved at 4 hours after administration is at least about 20%® lower than the Cmax and/or AUC achieved at 4 hours after administration of a comparable composition in an intact dosage form of equal drug dosage of the administered at least one piece.

22. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of: polyacrylates or copolymers thereof, and mixtures thereof; and a diffusion layer substantially covering the barrier layer and comprising a drug, and a diffusion polymer selected from the group consisting of: quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers, and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer comprises about 1 to 30% of the total thickness of the composition, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the rate of drug released from the dosage form at 4 hours after administration is substantially the same as the rate of drug released at 4 hours after administration from a comparable composition in an intact dosage form of equal drug dosage of the administered at least one piece,

and wherein the drug is an opioid.

23. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of: polyacrylates or copolymers thereof, and mixtures thereof; and a diffusion layer substantially covering the barrier layer and comprising a drug and a diffusion polymer selected from the group consisting of: quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic, polymers, acrylic or methacrylic copolymers, and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer comprises about 1 to 30% of the total thickness of the composition, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

wherein when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the Tmax achieved after administration is substantially the same or greater than the Tmax achieved after administration of a comparable composition in an intact dosage form of equal drug dosage of the administered at least one piece,

and the drug is an opioid.

24. The pharmaceutical composition of claim 23 , wherein the Tmax achieved after administration is at least about 20% greater than the Tmax achieved after administration of comparable composition in an intact dosage form of equal drug dosage of the administered at least one piece.

25. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of: polyacrylates or copolymers thereof and mixtures thereof; and a diffusion layer substantially covering the barrier layer and comprising a drug and a diffusion polymer selected from the group consisting of: quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers, and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer comprises about 1 to 30% of the total thickness of the composition, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

wherein when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the Cmax and/or AUC achieved at 4 hours after administration is substantially the same or lower than the Cmax and/or AUC achieved at 4 hours after administration of an intact dosage form of a bioequivalent drug composition, wherein the drug dosage in the intact dosage form of the bioequivalent drug composition is equal to the drug dosage of the administered at least one piece,

and wherein the drug is an opioid.

26. The pharmaceutical composition of claim 25 , wherein the Cmax and/or AUC achieved at 4 hours after administration is at least about 20% lower than the Cmax and/or AUC achieved at 4 hours after administration of the intact dosage form of the bioequivalent drug composition.

27. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of: polyacrylates or copolymers thereof, and mixtures thereof; and a diffusion layer substantially covering the barrier layer and comprising a drug and a diffusion polymer selected from the group consisting of: quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers, and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer comprises about 1 to 30% of the total thickness of the composition, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

wherein when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the rate of drug released from the dosage form at 4 hours after administration is substantially the same or lower than the rate of drug released at 4 hours after administration from an intact dosage form of a bioequivalent drug composition, wherein the drug dosage in the intact dosage form of the bioequivalent drug composition is equal to the drug dosage of the administered at least one piece,

and wherein the drug is an opioid.

28. The pharmaceutical composition of claim 27 , wherein the rate of drug released from the composition at 4 hours after administration is at least about 20% lower than the rate of drug released at 4 hours after administration from the intact dosage form of the bioequivalent drug composition.

29. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of: polyacrylates or copolymers thereof and mixtures thereof; and a diffusion layer substantially covering the barrier layer and comprising a drug and a diffusion polymer selected from the group consisting of: quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers, and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer comprises about 1 to 30% of the total thickness of the composition, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

wherein when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the Tmax achieved after administration is substantially the same or greater than the Tmax achieved administration of an intact dosage form of a bioequivalent drug composition, wherein the drug dosage in the intact dosage form of the bioequivalent drug composition is equal to the drug dosage of the administered at least one piece,

and wherein the drug is an opioid.

30. The pharmaceutical composition of claim 29 , wherein the Tmax achieved after administration is at least about 20% greater than the Tmax achieved after administration of the intact dosage form, of the bioequivalent drug composition.

31. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of; polyacrylates or copolymers thereof and mixtures thereof; and a diffusion layer substantially covering the barrier layer and comprising a drug and a diffusion polymer selected from the group consisting of: quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers, and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug, is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer comprises about 1 to 30% of the total thickness of the composition, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

wherein when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the Cmax and/or AUC achieved at 4 hours after administration is substantially the same or lower than the Cmax and/or AUC achieved at 4 hours after administration of a divided piece of a bioequivalent drug composition, wherein the divided piece of the bioequivalent drug composition comprises a drug, dosage equal to the drug dosage of the administered at least one piece, and

wherein the drug is an opioid.

32. The pharmaceutical composition of claim 31 , wherein the Cmax and/or AUC achieved at 4 hours after administration is at least about 20% lower than the Cmax and/or AUC achieved at 4 hours after administration of a divided piece of a bioequivalent drug composition, wherein the divided piece of the bioequivalent drug composition comprises a drug dosage equal to the drug dosage of the administered at least one piece.

33. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of: polyacrylates or copolymers thereof and mixtures thereof; and a diffusion layer substantially covering the barrier layer and comprising a drug and a diffusion polymer selected from the group consisting of: quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers, and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer comprises about 1 to 30% of the total thickness of the composition, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

wherein when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the rate of drug released from the dosage form at 4 hours after administration is substantially the same or lower than the rate of drug released at 4 hours after administration from a divided piece of a bioequivalent drug composition, wherein the divided piece of the bioequivalent drug composition comprises a drug dosage equal to the drug dosage of the administered at least one piece

and wherein the drug is an opioid.

34. The pharmaceutical composition of claim 33 , wherein the rate of drug released from the composition at 4 hours after administration is at least about 20% lower than the rate of drug released at 4 hours after administration from a divided piece of a bioequivalent drug composition, wherein the divided piece of the bioequivalent drug composition comprises a drug dosage equal to the drug dosage of the administered at least one piece.

35. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of: polyacrylates or copolymers thereof and mixtures thereof; and a diffusion layer substantially covering the barrier layer and comprising a drug and a diffusion polymer selected from the group consisting of: quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers, and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer comprises about 1 to 30% of the total thickness of the composition, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

wherein when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the Tmax achieved after administration is substantially the same or greater than the Tmax achieved after administration of a divided piece of a bioequivalent drug composition, wherein the divided piece of the bioequivalent drug composition comprises a drug dosage equal to the drug dosage of the administered at least one piece,

and wherein the drug is an opioid.

36. The pharmaceutical composition of claim 35 , wherein the Tmax achieved after administration is at least about 20% greater than the Tmax achieved after administration of a divided piece of a bioequivalent drug composition, wherein the divided piece of the bioequivalent drug composition comprises a drug dosage equal to the drug dosage of the administered at least one piece.

37. An oral pharmaceutical composition comprising a monolithic dosage form,

wherein the dosage form comprises an inner expansion layer comprising an expansion polymer; a barrier layer substantially covering the expansion layer and comprising a barrier polymer selected from the group consisting of: polyacrylates or copolymers thereof and mixtures thereof; and, a diffusion layer substantially covering the barrier layer and comprising a drug and a diffusion polymer selected from the group consisting of: quarternary ammonium acrylic or methacrylic polymers, acrylic or methacrylic polymers, acrylic or methacrylic copolymers, and mixtures thereof, wherein the barrier layer is bonded to the diffusion layer, and the barrier layer and diffusion layer are cured, and wherein the drug is substantially homogeneously distributed within the diffusion polymer and diffuses from the diffusion layer within the gastrointestinal tract, wherein the diffusion layer comprises about 1 to 30% of the total thickness of the composition, and

wherein the dosage form is divided into more than one piece, the bond between the diffusion layer and barrier layer is substantially preserved, and

wherein when the dosage form is divided into more than one piece and at least one of the pieces is administered to a subject, the rate of drug released from the dosage form at 4 hours after administration is at least about 10% lower than the rate of drug released at 4 hours after administration from a comparable composition in an intact dosage form of equal drug dosage of the administered at least one piece,

and wherein the drug is an opioid.

38. The pharmaceutical composition of claim 37 , wherein the rate of drug released from the composition at 4 hours after administration is at least about 20% lower than the rate of drug released at 4 hours after administration from a comparable composition in an intact dosage form of equal drug dosage of the administered at least one piece.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

64. The pharmaceutical composition of claim 10 , wherein the drug is hydrocodone.

65. The pharmaceutical composition of claim 10 , wherein the drug is morphine.

66. The pharmaceutical composition of claim 10 , wherein the drug is oxycodone.

67. The pharmaceutical composition of claim 10 , wherein the drug is hydromorphone.

68. The pharmaceutical composition of claim 10 , wherein the drug is oxymorphone.

69. The pharmaceutical composition of claim 12 , wherein the drug is hydrocodone.

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

71. The pharmaceutical composition of claim 12 , wherein the drug is oxycodone.

72. The pharmaceutical composition of claim 12 , wherein the drug is hydromorphone.

73. The pharmaceutical composition of claim 12 , wherein the drug is oxymorphone.

74. The pharmaceutical composition of claim 14 , wherein the drug is hydrocodone.

75. The pharmaceutical composition of claim 14 , wherein the drug is morphine.

76. The pharmaceutical composition of claim 14 , wherein the drug is oxycodone.

77. The pharmaceutical composition of claim 14 , wherein the drug is hydromorphone.

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

79. The pharmaceutical composition of claim 16 , wherein the drug is hydrocodone.

80. The pharmaceutical composition of claim 16 , wherein he drug is morphine.

81. The pharmaceutical composition of claim 16 , wherein the drug is oxycodone.

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

83. The pharmaceutical composition of claim 16 , wherein the drug is oxymorphone.

84. The pharmaceutical composition of claim 18 , wherein the drug is hydrocodone.

85. The pharmaceutical composition of claim 18 , wherein the drug is morphine.

86. The pharmaceutical composition of claim 18 , wherein the drug is oxycodone.

87. The pharmaceutical composition of claim 18 , wherein the drug is hydromorphone.

88. The pharmaceutical composition of claim 18 , wherein the drug is oxymorphone.

89. The pharmaceutical composition of claim 20 , wherein the drug is hydrocodone.

90. The pharmaceutical composition of claim 20 , wherein the drug is morphine.

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

92. The pharmaceutical composition of claim 20 , wherein the drug is hydromorphone.

93. The pharmaceutical composition of claim 20 , wherein the drug is oxymorphone.

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

95. The pharmaceutical composition of claim 22 , wherein the drug is morphine.

96. The pharmaceutical composition of claim 22 , wherein the drug is oxycodone.

97. The pharmaceutical composition of claim 22 , wherein the drug is hydromorphone.

98. The pharmaceutical composition of claim 22 , wherein the drug is oxymorphone.

99. The pharmaceutical composition of claim 23 , wherein the drug is hydrocodone.

100. The pharmaceutical composition of claim 23 , wherein the drug is morphine.

101. The pharmaceutical composition of claim 23 , wherein the drug is oxycodone.

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

103. The pharmaceutical composition of claim 23 , wherein the drug is oxymorphone.

104. The pharmaceutical composition of claim 25 , wherein the drug is hydrocodone.

105. The pharmaceutical composition of claim 25 , wherein the drug is morphine.

106. The pharmaceutical composition of claim 25 , wherein the drug is oxycodone.

107. The pharmaceutical composition of claim 25 , wherein the drug is hydromorphone.

108. The pharmaceutical composition of claim 25 , wherein the drug is oxymorphone.

109. The pharmaceutical composition of claim 27 , wherein the drug is hydrocodone.

110. The pharmaceutical composition of claim 27 , wherein the drug is morphine.

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

112. The pharmaceutical composition of claim 27 , wherein the drug is hydromorphone.

113. The pharmaceutical composition of claim 27 , wherein the drug is oxymorphone.

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

115. The pharmaceutical composition of claim 29 , wherein the drug is morphine.

116. The pharmaceutical composition of claim 29 , wherein the drug is oxycodone.

117. The pharmaceutical composition of claim 29 , wherein the drug is hydromorphone.

118. The pharmaceutical composition of claim 29 , wherein the drug is oxymorphone.

119. The pharmaceutical composition of claim 31 , wherein the drug is hydrocodone.

120. The pharmaceutical composition of claim 31 , wherein the drug is morphine.

121. The pharmaceutical composition of claim 31 , wherein the drug is oxycodone.

122. The pharmaceutical composition of claim 31 , wherein the drug is hydromorphone.

123. The pharmaceutical composition of claim 31 , wherein the drug is oxymorphone.

124. The pharmaceutical composition of claim 33 , wherein the drug is hydrocodone.

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

126. The pharmaceutical composition of claim 33 , wherein the drug is oxycodone.

127. The pharmaceutical composition of claim 33 , wherein the drug is hydromorphone.

128. The pharmaceutical composition of claim 33 , wherein the drug is oxymorphone.

129. The pharmaceutical composition of claim 35 , wherein the drug is hydrocodone.

130. The pharmaceutical composition of claim 35 , wherein the drug is morphine.

131. The pharmaceutical composition of claim 35 , wherein the drug is oxycodone.

132. The pharmaceutical composition of claim 35 , wherein the drug is hydromorphone.

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

134. The pharmaceutical composition of claim 37 , wherein the hydrocodone.

135. The pharmaceutical composition of claim 37 , wherein the drug is morphine.

136. The pharmaceutical composition of claim 37 , wherein the drug is oxycodone.

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

138. The pharmaceutical composition of claim 37 , wherein the drug is oxymorphone.