Comparing the Effect of Tampering on the Oral Pharmacokinetic Profiles of Two Extended‐Release Oxycodone Formulations with Abuse‐Deterrent Properties

Objective Oxycodone DETERx® is an extended‐release (ER), microsphere‐in‐capsule abuse‐deterrent‐formulation designed to retain its extended‐release properties following tampering or misuse (e.g., chewing, crushing). This study assessed the safety and pharmacokinetics of orally administered intact and crushed Oxycodone DETERx® capsules compared with intact and crushed reformulated OxyContin® tablets and crushed immediate‐release oxycodone tablets (IR oxycodone). Methods This was a randomized, open‐label, active‐controlled, cross‐over study. Healthy subjects received five oxycodone treatments (40 mg) with a standardized high‐fat, high‐calorie meal: Oxycodone DETERx® (intact or crushed), OxyContin® (intact or crushed), and IR oxycodone (crushed). Blood samples were collected for assessment of oxycodone plasma concentrations. Results Thirty‐eight subjects completed the study. Both crushed and intact Oxycodone DETERx® resulted in lower peak plasma concentrations when compared with IR oxycodone. Crushed Oxycodone DETERx® was bioequivalent to intact Oxycodone DETERx® and exhibited a numerically lower Cmax. Also, median Tmax was unchanged by crushing. In contrast, mean peak plasma oxycodone concentrations for crushed OxyContin® were significantly higher compared with intact OxyContin® and were bioequivalent to IR oxycodone. Median Tmax for crushed OxyContin® was the same as IR oxycodone and 3.25 hours shorter than intact OxyContin®. Conclusions These data demonstrate that when crushed and taken orally, Oxycodone DETERx® maintains its EXTENDED‐release profile, while crushed OxyContin® shows a pharmacokinetic profile similar to an immediate‐release product. These results suggest that Oxycodone DETERx® may be less attractive to illicit drug users compared with existing abuse‐deterrent‐formulations, while providing a safer option for patients who may unknowingly crush their medication such as those who have difficulty swallowing.