Assessment of a formulation designed to be crush-resistant in prescription opioid abusers

Abstract

Background The extent of intranasal and intravenous prescription opioid abuse has led to the development of formulations that are difficult to crush. The purpose of the present studies was to examine whether experienced prescription opioid abusers (individuals who were using prescription opioids for non-medical purposes regardless of how they were obtained) were able to prepare a formulation of oxymorphone hydrochloride ER 40 mg designed to be crush-resistant (DCR) for intranasal (Study 1) or intravenous abuse (Study 2), utilizing a non-crush-resistant formulation of oxymorphone (40 mg; OXM) as a positive control. Methods No drug was administered in these studies. Participants were provided with DCR and OXM tablets in random order and asked to prepare them for abuse with tools/solutions that they had previously requested. The primary outcome for Study 1 was particle size distribution, and the primary outcome for Study 2 was percent yield of active drug in the extracts. Other descriptive variables were examined to better understand potential responses to these formulations. Results Fewer DCR than OXM particles were smaller than 1.705 mm (9.8% vs. 97.7%), and thus appropriate for analyses. Percent yield of active drug in extract was low and did not differ between the two formulations (DCR: 1.95%; OXM: 1.29%). Most participants were not willing to snort (92%) or inject (84%) the tampered products. Participants indicated that they found less relative value in the DCR than the OXM formulation across both studies. Conclusions Although there are safety issues associated with formulations that gel, these data suggest that the oxymorphone DCR formulations may be a promising technology for reducing opioid abuse.

Examining the Relationship between Social Context and Prescription Opioid Initiation Routes among Young Adults Entering Medical Detoxification

“…Our results also point to the potential utility of abuse deterrent drug formulations to prevent tampering [11,12,[29][30][31]. Despite these developments which may be useful in decreasing the misuse of POs, [11,29,31], it is difficult to determine whether these formulations actually cause decreases in PO misuse overall; ours and other published results suggest that PO misusers shift to non-abuse deterrent formulations or to heroin due to its increased availability, ease of use, and cheaper cost [29].…”

“…Despite these developments which may be useful in decreasing the misuse of POs, [11,29,31], it is difficult to determine whether these formulations actually cause decreases in PO misuse overall; ours and other published results suggest that PO misusers shift to non-abuse deterrent formulations or to heroin due to its increased availability, ease of use, and cheaper cost [29]. Given the high rates of initiation through tampering among our sample, the broader use of abuse deterrent formulations could have a significant impact on drug use escalation among youth.…”

Commercial Abuse-Deterrent Dosage Forms: Clinical Status

“…The study may also go further and determine the drug concentration in the volume obtained. For example, a study of crush resistant oxymorphone ER tablets (Opana® ER) looked at the ability of experienced abusers to make the product into a form abusable by intravenous injection using as much tools, time, and materials they requested [17]. The extract, if produced, was collected by the investigators and the percent yield of extracted oxymorphone was determined as the primary outcome.…”

Abuse-Deterrent Formulations, an Evolving Technology Against the Abuse and Misuse of Opioid Analgesics

“…The reformulated OX-ER utilizes an extrusion process including the polyethylene oxide INTAC matrix offering certain physical and physicochemical tamper-resistant properties. The tablet is difficult to crush and will turn into a viscous gel when combined with fluids [27].…”