Mayock Stephen P, Saim Said, Fleming Alison B
Collegium Pharmaceutical, Inc., 780 Dedham St, Ste 800, Canton, MA, 02021, USA.
Clin Drug Investig. 2017 Dec;37(12):1117-1124. doi: 10.1007/s40261-017-0561-9.
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 DETERx (Xtampza ER, Collegium Pharmaceutical, Inc., Canton, MA, USA) and other commercially available ER opioid formulations with and without physicochemical abuse-deterrent characteristics to be manipulated by crushing in an in vitro setting.
In vitro dissolution techniques were used to compare the opioid release from a variety of ER opioid formulations. Dissolution was assessed for intact and crushed dosage forms. Opioid release was quantified using high-performance liquid chromatography.
Intact formulations exhibited drug release rates characteristic of 12- or 24-h dosage forms. After crushing using commonly available household tools, only Xtampza ER maintained ER of opioid.
Xtampza ER maintained its ER characteristics after crushing, unlike many other commercially available opioid formulations, including some formulated with abuse-deterrent properties. As such, Xtampza ER may be less appealing to abusers and offer a margin of safety for patients who manipulate dosage forms to facilitate swallowing.
缓释（ER）阿片类药物与高滥用率相关。娱乐性阿片类药物使用者常常对ER制剂进行处理，以便在短时间内达到高血浆浓度，从而产生更快且更强烈的欣快感。患者也可能会处理ER片剂以方便吞咽，但并未意识到这样做可能会增加释放速率。本研究的目的是评估羟考酮DETERx（Xtampza ER，美国马萨诸塞州坎顿市Collegium制药公司）以及其他具有或不具有物理化学滥用威慑特性的市售ER阿片类药物制剂在体外环境下被碾碎处理的可能性。
采用体外溶出技术比较多种ER阿片类药物制剂的阿片类药物释放情况。对完整剂型和碾碎剂型的溶出情况进行评估。使用高效液相色谱法定量阿片类药物释放量。
完整制剂呈现出12小时或24小时剂型特有的药物释放速率。使用常见家用工具碾碎后，只有Xtampza ER维持了阿片类药物的缓释特性。
与许多其他市售阿片类药物制剂不同，包括一些具有滥用威慑特性的制剂，Xtampza ER在碾碎后仍保持其缓释特性。因此，Xtampza ER可能对滥用者吸引力较小，并为那些处理剂型以方便吞咽的患者提供一定的安全边际。
