DETERx™ Tamper-Resistance

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Extensive Testing
Collegium has conducted an extensive battery of in vitro and in vivo tampering tests to assess the characteristics of the DETERx™ Technology.

Chewing studies
Collegium has studied the effect of tampering with DETERx™ beads via chewing in two independent clinical studies. Both studies confirmed that chewing does not compromise the time-release mechanism of the formulation. The plasma profile for the chewed dosage form was bioequivalent to DETERx™ (90% confidence intervals within 80-125%) when administered whole and as intended.  In fact, the maximum plasma concentration was slightly lower when the formulation was chewed than when it was administered intact.  Thus, misuse by chewing does not result in a spike in plasma level as desired by the abuser.
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Crushing
The DETERx™ formulation was crushed using multiple techniques and compared to a conventional extended release opioid tablet. After crushing, both products were subjected to a variety of household solvents to compare the ‘dose dumping’ that may occur. The impact of crushing was determined by measuring the median particle size via laser diffraction.  The effectiveness of crushing was significantly greater for conventional extended release tablets than for the novel DETERx™ formulation.  The influence of crushing on drug release was characterized for the worst case scenario (mortar & pestle).  In contrast to conventional extended release tablets, DETERx™ beads maintain their time-release in common solvents after crushing with a mortar and pestle.

Extraction studies
Collegium has developed an extensive battery of tests to assess the various methods commonly employed by opioid abusers to defeat the time release system of ER opioids. Collegium has studied COL-003 in solvent extraction studies intended to measure the amount of active drug that can be extracted from the formulation using various solvents under different conditions to fully characterize the tamper resistant properties of the formulation.  The DETERx™ formulation prevented drug from “dose dumping” in a range of common solvents, even after crushing the beads.

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Syringability
The feasibility of syringing the DETERx™ formulation was assessed. DETERx™ beads were melted at a high temperature and drawn up into a syringe. Due to the high melting point, the formulation solidified while drawing it up into the syringe, demonstrating the resistance of the formulation to direct injection of the melt.
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