Pharmaceutical compositions configured to deter dosage form splitting

Abstract

An oral pharmaceutical composition comprising a drug and one or more pharmaceutically acceptable excipients in a monolithic dosage form, wherein the dosage form is configured such that 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, AUC, and/or rate of drug released after administration is substantially the same or lower and the Tmax is higher than the Cmax, AUC, rate of drug released, and/or Tmax after administration of: (1) a comparable composition in intact dosage form of equal drug dosage of the administered at least one piece; (2) a bioequiva lent drug composition in an intact dosage form of equal drug dosage to the administered at least one piece; and (3) a divided piece of a bioequivalent drug composition, wherein the divided piece comprises a drug dosage equal to the dosage of the administered piece of the oral composition. Methods of making the same and methods of using the same are also provided.

What is claimed: 
     
         1 . An oral pharmaceutical composition, comprising a drug and one or more pharmaceutically acceptable excipients in a monolithic dosage form, wherein the dosage form is configured such that 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 after a time period selected from the group consisting of 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours after administration is substantially the same or lower than the Cmax and/or AUC achieved after administration of a comparable composition in an intact dosage form of equal drug dosage of the administered at least one piece. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the Cmax and/or AUC achieved after a time period selected from the group consisting of 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours after administration, is at least about 20% lower than the Cmax and/or AUC achieved 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 drug and one or more pharmaceutically acceptable excipients a monolithic dosage form, wherein the dosage form is configured such that 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 within a time period selected from the group consisting of 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours after administration is substantially the same or lower than the rate of drug released from a comparable composition in an intact dosage form of equal drug dosage of the administered at least one piece. 
     
     
         4 . The pharmaceutical composition of  claim 3 , wherein the rate of drug released from the composition within a time period selected from the group consisting of 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours after administration is at least about 20% lower than the rate of drug released from a comparable composition in an intact dosage form of equal drug dosage of the administered at least one piece. 
     
     
         5 . An oral pharmaceutical composition, comprising a drug and one or more pharmaceutically acceptable excipients in a monolithic dosage form, wherein the dosage form is configured such that 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. 
     
     
         6 . The pharmaceutical composition of  claim 5 , 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. 
     
     
         7 . An oral pharmaceutical composition, comprising a drug and one or more pharmaceutically acceptable excipients in a monolithic dosage form, wherein the dosage form is configured such that 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 after a time period selected from the group consisting of 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours after administration is substantially the same or lower than the Cmax and/or AUC achieved 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. 
     
     
         8 . The pharmaceutical composition of  claim 7 , wherein the Cmax and/or AUC achieved after a time period selected from the group consisting of 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 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. 
     
     
         9 . An oral pharmaceutical composition, comprising a drug and one or more pharmaceutically acceptable excipients in a monolithic dosage form, wherein the dosage form is configured such that 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 within a time period selected from the group consisting of 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 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, 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. 
     
     
         10 . The pharmaceutical composition of  claim 9 , wherein the rate of drug released from the composition within a time period selected from the group consisting of 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 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. 
     
     
         11 . An oral pharmaceutical composition, comprising a drug and one or more pharmaceutically acceptable excipients in a monolithic dosage form, wherein the dosage form is configured such that 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. 
     
     
         12 . The pharmaceutical composition of  claim 11 , 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. 
     
     
         13 . An oral pharmaceutical composition, comprising a drug and one or more pharmaceutically acceptable excipients in a monolithic dosage form, wherein the dosage form is configured such that 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 after a time period selected from the group consisting of 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours after administration is substantially the same or lower than the Cmax and/or AUC 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. 
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein the Cmax and/or AUC achieved after a time period selected from the group consisting of 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours after administration, is at least about 20% lower than the Cmax and/or AUC 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. 
     
     
         15 . An oral pharmaceutical composition, comprising a drug and one or more pharmaceutically acceptable excipients in a monolithic dosage form, wherein the dosage form is configured such that 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 within a time period selected from the group consisting of 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours after administration is substantially the same or lower than the rate of drug released 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 . The pharmaceutical composition of  claim 15 , wherein the rate of drug released from the composition within a time period selected from the group consisting of 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 12 hours, 16 hours, and 24 hours after administration is at least about 20% lower than the rate of drug released 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. 
     
     
         17 . An oral pharmaceutical composition, comprising a drug and one or more pharmaceutically acceptable excipients in a monolithic dosage form, wherein the dosage form is configured such that 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. 
     
     
         18 . The pharmaceutical composition of  claim 17 , 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.