Tamper-resistant oral opioid agonist formulations

An oral dosage form comprising (i) an opioid agonist in releasable form and (ii) a sequestered opioid antagonist which is substantially not released when the dosage form is administered intact, such that the ratio of the amount of antagonist released from said dosage form after tampering to the amount of said antagonist released from said intact dosage form is about 4:1 or greater, based on the in-vitro dissolution at 1 hour of said dosage form in 900 ml of Simulated Gastric Fluid using a USP Type II (paddle) apparatus at 75 rpm at 37 degrees C. wherein said antagonist is in the form of multiparticulates individually coated with a sequestering material which substantially prevents release of the antagonist.

An oral dosage form comprising (i) an opioid agonist in releasable form and (ii) a sequestered opioid antagonist which is substantially not released when the dosage form is administered intact, such that the ratio of the amount of antagonist released from said dosage form after tampering to the amount of said antagonist released from said intact dosage form is about 4:1 or greater, based on the in-vitro dissolution at 1 hour of said dosage form in 900 ml of Simulated Gastric Fluid using a USP Type II (paddle) apparatus at 75 rpm at 37 degrees C. wherein said antagonist is dispersed in a matrix comprising a sequestering material which substantially prevents the release of the antagonist.

An oral dosage form comprising (i) an opioid agonist in releasable form and (ii) a sequestered opioid antagonist which is substantially not released when the dosage form is administered intact, such that the ratio of the amount of antagonist contained in said intact dosage form to the amount of said antagonist released from said intact dosage form after 1 hour is about 4:1 or greater, based on the in-vitro dissolution at 1 hour of said dosage form in 900 ml of Simulated Gastric Fluid using a USP Type II (paddle) apparatus at 75 rpm at 37 degrees C. wherein said agonist and antagonist are interdispersed and are not isolated from each other in two distinct layers.

An oral dosage form comprising (i) an opioid agonist in a releasable form;

• and (ii) a sequestered opioid antagonist which is substantially not released when the dosage form is administered intact, such that the amount of antagonist released from said intact dosage form after 1 hour is less than an amount bioequivalent to 0.25 mg naltrexone and the amount of said antagonist released after 1 hour from said dosage form after tampering is an amount bioequivalent to 0.25 mg naltrexone or more, said release based on the dissolution at 1 hour of said dosage from in 900 ml of Simulated Gastric Fluid using a USP Type II (paddle) apparatus at 75 rpm at 37 degrees C., wherein said agonist and antagonist are interdispersed and are not isolated from each other in two distinct layers.

An oral dosage form comprising (i) an opioid agonist in a releasable form;

• and (ii) sequestered naltrexone or a pharmaceutically acceptable sat thereof which is substantially not released when the dosage form is administered intact, such that the amount of naltexone released from said intact dosage form after 1 hour is less than 0.25 mg and the amount of said naltrexone released after 1 hour from said dosage form after tampering is 0.25 mg or more, said release based on the dissolution at 1 hour of said dosage form in 900 ml of Simulated Gastric Fluid using a USP Type II (paddle) apparatus at 75 rpm at 37 degrees C., wherein said agonist and naltrexone are interdispersed and are not isolated from each other in two distinct layers.

An oral dosage form comprising (i) a therapeutic effect of an opioid agonist;

• and (ii) a sequestered opioid antagonist, such that at 1 hour after oral administration, said dosage form releases not more than 25% of said antagonist, said dosage form providing analgesia and said released antagonist not affecting analgesic efficacy, wherein said agonist and antagonist are interdispersed and are not isolated from each other in two distinct layers.

An oral dosage form comprising:

• (i) an opioid agonist in a releasable form;
• and an (ii) opioid antagonist in substantially non-releasable form wherein said antagonist is in the form of multiparticulates individually coated with a material that substantially prevents release of the antagonist.

An oral dosage form comprising:

• (i) an opioid agonist in a releasable form;
• and an (ii) opioid antagonist in substantially non-releasable form wherein said antagonist is dispersed in a matrix comprising a material that substantially prevents the release of the antagonist.

A dosage form comprising:

• (a) an opioid agonist;
• and
• (b) an orally-bioavailable opioid antagonist in a substantially non-releasable form;

A method of preparing an oral dosage form comprising pretreating an opioid antagonist to render it substantially non-releasable;

• and combining the pretreated antagonist with a releasable form of an opioid agonist.