Mechanical Characterization of Thermally Annealed Tablets Containing Polyethylene Oxide for Abuse Deterrence.

The abuse of prescription opioid drugs is a well-documented and very serious problem. One of the typical first steps an abuser will take is to manipulate a tablet into to a fine powder. To deter this behavior, formulators use crush-resistant technologies like polyethylene oxide (PEO). When heat-treated, PEO creates a hard, flexible tablet that cannot be easily ground down into a fine powder. We investigated the effects of PEO molecular weight (MW), annealing temperature, and annealing time on tablet compression deformation behavior and fracture resistance. These tests were designed to represent an abuser's attempt to smash and grind a tablet, respectively. Annealing temperatures above the melting point of PEO showed the most improvement in mechanical properties compared with that in unannealed tablets. The minimum annealing time was dependent on the polymer MW and annealing temperature. Tablets were manipulated using a coffee grinder, and the particle size of the resulting powders was measured. The particle size correlated well with fracture toughness, demonstrating that increasing fracture toughness increases the manipulation resistance of a PEO tablet.

Direct measurement of the time-dependent mechanical response of HPMC and PEO compacts during swelling.

Mechanical indentation is used to measure the time dependent mechanical properties of three model compact formulations during swelling in aqueous media. The formulations are based on polyethylene oxide (PEO), hydroxypropyl methylcellulose (HPMC) and a PEO/HPMC blend. The technique is sensitive to changes in compact thickness and mechanical response and is used to characterize changes in the mechanical properties of the model compacts during the swelling process. The gel thickness and the effective elastic modulus of the gel layer are obtained from the load/displacement relationship during initial indentation. The HPMC and hybrid compacts showed significantly more swelling (110%) than the PEO compact (67%). Viscoelastic properties of the gel layer are determined throughout the swelling process by an oscillatory indentation method. Results show the complex modulus of all three compacts decreasing by approximately an order of magnitude over the course of swelling for 6h. The measurement techniques presented here can easily be extended to more complex systems.