OBJECTIVE: To prepare a polyethylene oxide-based tablet with high mechanical strength that would release an opioid for once- or twice-daily administration. This tablet would also create barriers against crushing and subsequent preparation steps for abuse and misuse that are not present in conventional opioid formulations. RESEARCH DESIGN & METHODS: Innovative manufacturing processes were created by applying heat and force simultaneously, using tramadol HCl as model compound; production scale testing used oxymorphone HCl. Standardized in vitro crush force and extraction tests were performed. RESULTS & DISCUSSION: A production scale manufacturing process using hot melt extrusion of a strand, cooling, slicing and shaping the slices into tablet form produced stable oxymorphone extended-release (ER) tablets with in vitro dissolution characteristics similar to commercial oxymorphone ER. The tablets resisted crushing by spoons, pill crushers and a hammer and resisted extraction in a test battery of solvents. The standardized tampering methods used here do not include all methods an abuser might employ. Postmarketing data will be needed to determine the actual impact of tamper resistance mechanisms on opioid abuse rates. CONCLUSIONS: This purely mechanical approach to tamper resistance may make a tablet less attractive for abuse without exposing compliant patients to new risks associated with opioid antagonists or aversive compounds. A compliant patient's risk of adverse events may be reduced by the tablet's resistance to accidental crushing.
OBJECTIVE: To prepare a polyethylene oxide-based tablet with high mechanical strength that would release an opioid for once- or twice-daily administration. This tablet would also create barriers against crushing and subsequent preparation steps for abuse and misuse that are not present in conventional opioid formulations. RESEARCH DESIGN & METHODS: Innovative manufacturing processes were created by applying heat and force simultaneously, using tramadol HCl as model compound; production scale testing used oxymorphone HCl. Standardized in vitro crush force and extraction tests were performed. RESULTS & DISCUSSION: A production scale manufacturing process using hot melt extrusion of a strand, cooling, slicing and shaping the slices into tablet form produced stable oxymorphone extended-release (ER) tablets with in vitro dissolution characteristics similar to commercial oxymorphone ER. The tablets resisted crushing by spoons, pill crushers and a hammer and resisted extraction in a test battery of solvents. The standardized tampering methods used here do not include all methods an abuser might employ. Postmarketing data will be needed to determine the actual impact of tamper resistance mechanisms on opioid abuse rates. CONCLUSIONS: This purely mechanical approach to tamper resistance may make a tablet less attractive for abuse without exposing compliant patients to new risks associated with opioid antagonists or aversive compounds. A compliant patient's risk of adverse events may be reduced by the tablet's resistance to accidental crushing.