In Vitro Drug Release After Crushing: Evaluation of Xtampza® ER and Other ER Opioid Formulations

Abstract

Background and Objective Extended-release (ER) opioids are associated with high rates of abuse. Recreational opioid users often manipulate ER formulations to achieve a high plasma concentration in a short amount of time, resulting in a more rapid and intense high. Patients may also manipulate ER tablets to facilitate swallowing, without recognizing that manipulation could increase release rate. The goal of this study was to assess the ability of oxycodone

Mitigation of IV Abuse Through the Use of Abuse‐Deterrent Opioid Formulations: An Overview of Current Technologies

“…The dissolution profiles and ER properties remained relatively intact after the physical manipulation of oxycodone DETERx, whereas greater changes to the dissolution profile were observed after the physical manipulation of oxycodone OP . Similarly, crushing oxycodone DETERx with common household tools resulted in the release of just 10% more opioid relative to intact drug after 15 minutes of dissolution; in comparison, oxycodone OP released slightly less than 60% more opioid, and other non‐ADF ER formulations released ≥60% more opioid relative to intact drug after 15 minutes of dissolution . Oxycodone DETERx was the only ER opioid to maintain a slow release of study drug early in the dissolution time course after physical manipulation …”

“…Abuse‐deterrent formulations of opioid medications were designed primarily to mitigate the abuse of prescription opioids by both recreational and experienced drug abusers . In addition, ADFs are intended to provide protection for patients with chronic pain who unwittingly (eg, crushing large tablets to make them easier to swallow) or intentionally (eg, to enhance pain relief or other desirable effects) attempt to manipulate opioid medications . Table summarizes the approaches for achieving abuse deterrence .…”

“…For some ADFs, more detailed results of in vitro laboratory studies relevant to IV abuse potential are available from publications and congress presentations. Table summarizes the findings of category 1 testing for ER/LA opioids with FDA‐approved ADF labeling …”

Comment on Mayock SP, Saim S, Fleming AB. In Vitro Drug Release After Crushing: Evaluation of Xtampza® ER and Other ER Opioid Formulations

“…The publication by Mayock et al [ 1 ] provides incomplete information that may leave your readership with a false sense of security regarding the expected performance and impact that the Xtampza ® ER formulation may have on abuse in the real world. In our opinion, the study authors present a biased and faulty study design that does not subject Xtampza ER to manipulation techniques most relevant to this product’s wax-based formulation.…”

Response to Crudele et al. Commentary on Mayock et al. “In Vitro Drug Release after Crushing: Evaluation of Xtampza® ER and Other ER Opioid Formulations”

“…We appreciate Crudele and Giordano [ 1 ] taking the time to read our publication “In Vitro Drug Release after Crushing: Evaluation of Xtampza® ER and Other ER Opioid Formulations” [ 2 ], which reported on the ability of oxycodone DETERx (Xtampza ER, Collegium Pharmaceutical, Inc., Canton, MA, USA) and other commercially available extended-release (ER) opioid formulations with and without physicochemical abuse-deterrent characteristics to be manipulated by crushing in an in vitro setting. We are grateful to the editors for a chance to respond to their comments.…”