Tamper resistant dosage form comprising co-extruded, sequestered adverse agent particles and process of making same

摘要

The present invention relates to co-extruded pharmaceutical compositions and dosage forms comprising an adverse agent, such as an opioid antagonist, which can be sequestered. The pharmaceutical compositions and dosage forms diversion of a dosage form containing an active pharmaceutical agent, such as an opioid. The present invention also relates to methods of treating a patient with such a dosage form, as well as kits containing such a dosage form with instructions for using the dosage form to treat a patient. The present invention further relates to a process for the preparation of such pharmaceutical compositions and dosage forms comprising co-extrusion of a core comprising an adverse agent and a sheath.

主权项

1. An oral dosage form comprising:
a plurality of controlled release extruded cylindrical first particles comprising a matrix comprising opioid agonist, wherein the first particles provide a controlled release of the opioid agonist in vivo over 12 hours or more upon oral administration to a patient: wherein the extruded cylindrical first particles are devoid of any opioid antagonist: and a plurality of sequestered co-extruded cylindrical second particles comprising a cylindrical core having a constant diameter along substantially its entire length and comprising a sequestering matrix comprising an opioid antagonist dispersed in a hydrophobic material and a co-axial sequestering sheath having a constant thickness along substantially its entire length and which radially surrounds the cylindrical core along the entire length of the core and leaves at least a portion of each end of the core uncovered by the sheath, wherein the sheath is substantially devoid of opioid antagonist; the core and the sheath are co-extruded through a co-axial co-extrusion die, the opioid antagonist is sequestered by the sequestering matrix, and the sheath and the co-extruded second particles exhibit an in vitro dissolution of opioid antagonist of less than 1% when tested using the USP Basket Method with a Type I basket, 100 rpm, 700 ml simulated gastric fluid, pH 1.2 without enzyme at 37° C. for 1 hour followed by 900 ml simulated intestinal fluid at 7.5 pH without enzyme; wherein the co-extruded cylindrical second particles are devoid of any opioid agonist, wherein the constant thickness of the co-axial sequestering sheath ranges from about 0.05 mm to about 2.95 mm, and wherein the controlled release extruded cylindrical first particles and the sequestered co-extruded cylindrical second particles each have a length ranging from about 0.1 mm to about 3.0 mm and a diameter ranging from about 0.1 mm to about 3.0 mm.