Fleming Alison B, Scungio Todd A, Grima Michael P, Mayock Stephen P
Collegium Pharmaceutical, Inc., Canton, Massachusetts.
J Opioid Manag. 2016 Jan-Feb;12(1):57-65. doi: 10.5055/jom.2016.0312.
Abuse of prescription analgesics is a well-recognized problem, with nearly 2 million people aged 12 years or older initiating nonmedical use of pain relievers in 2012. The prevalence of opioid abuse via intravenous (IV) injection has led to the development of dosage forms designed to deter abuse using different inactive ingredients and formulation strategies. This study evaluated the IV abuse potential for a novel, microsphere-encapsulated abuse-deterrent formulation of oxycodone, Xtampza™ ER (referred to as "oxycodone DETERx").
The extraction of oxycodone DETERx and two comparators, extended-release oxycodone (oxycodone ER) and immediate-release oxycodone (oxycodone IR), was evaluated in small volumes (5 and 10 mL) of water after manipulation of the dosage forms. The syringeability and injectability of these products were evaluated to determine the feasibility of using these products via IV injection.
The extraction of oxycodone from oxycodone DETERx was nominal, with <12 percent extracted under any test condition. Oxycodone ER and oxycodone IR had as much as 83 and 98 percent oxycodone extracted, respectively. Injectability and syringeability analyses showed that injection of oxycodone DETERx microspheres in suspension is not feasible. In contrast, oxycodone ER and oxycodone IR suspensions were more easily drawn into and expelled from a syringe. Furthermore, injection of molten oxycodone DETERx microspheres was also shown to be ineffective.
The chemical and physical properties of oxycodone DETERx provide barriers to manipulating the microspheres for the purpose of IV injection.
处方镇痛药滥用是一个公认的问题，2012年有近200万12岁及以上的人开始非医疗使用止痛剂。通过静脉注射滥用阿片类药物的情况促使人们开发了不同剂型，这些剂型采用不同的非活性成分和制剂策略来防止滥用。本研究评估了一种新型的、微球包裹的阿片类药物滥用威慑制剂——奥施康定缓释片（Xtampza™ ER，以下简称“奥施康定DETERx”）静脉注射滥用的可能性。
在对剂型进行处理后，评估了奥施康定DETERx以及两种对照品——缓释奥施康定（奥施康定ER）和速释奥施康定（奥施康定IR）在少量（5毫升和10毫升）水中的提取情况。对这些产品的可注射性和推注性进行了评估，以确定通过静脉注射使用这些产品的可行性。
奥施康定DETERx中奥施康定的提取量极少，在任何测试条件下提取量均低于12%。奥施康定ER和奥施康定IR的奥施康定提取量分别高达83%和98%。可注射性和推注性分析表明，注射悬浮状态的奥施康定DETERx微球是不可行的。相比之下，奥施康定ER和奥施康定IR的悬浮液更容易被吸入注射器并从注射器中推出。此外，注射熔融状态的奥施康定DETERx微球也被证明是无效的。
奥施康定DETERx的化学和物理性质为通过静脉注射目的操纵微球提供了障碍。
