Abuse-deterrent properties of REMOXY® ER, a high-viscosity extended-release oxycodone formulation
DOI:
https://doi.org/10.5055/jom.2018.0475Keywords:
opioid abuse, in vitro dissolution, injection, inhalationAbstract
Objective: These in vitro studies compared abuse-deterrent properties of REMOXY ER (extended-release oxycodone), a novel, high-viscosity gel formulation, versus the two currently marketed ER oxycodone formulations.
Methods: Tampering methods were tailored to each product to maximize oxycodone release with the least complexity, time, and effort, based on the physical/chemical properties of each formulation. Oral abuse was simulated by extracting oxycodone from each manipulated formulation in Common Ingestible Liquids and in Advanced Solvents (not ingestible and requiring additional separation). To simulate injection abuse, oxycodone was extracted from each manipulated formulation in low volumes of injection vehicles, heated or unheated. Inhalation abuse potential was assessed by volatilization.
Results: In oral abuse simulations, manipulated REMOXY ER released 2-22 percent of its oxycodone in 20 minutes in five Common Ingestible Liquids, versus 77-85 percent oxycodone released from OxyContin® ER in 5 minutes in four of the five. In six Advanced Solvents, REMOXY ER released 3-37 percent at 20 minutes, versus 55-89 percent released from OxyContin ER at 5 minutes. Minimal oxycodone was extracted from REMOXY ER in five injection vehicles, heated or unheated. In contrast, OxyContin ER released 65-87 percent of its oxycodone within 10 minutes in all vehicles, regardless of heating. Xtampza® ER released 96 percent of its oxycodone in a heated injection vehicle and released 50-60 percent in two unheated injection vehicles. Showing minimal inhalation abuse potential, 9 percent of oxycodone was vaporized from manipulated REMOXY ER at 20 minutes compared to 8.8 percent at 5 minutes for OxyContin ER.
Conclusions: In these studies, REMOXY ER demonstrated robust and meaningful abuse-deterrence relative to OxyContin ER and Xtampza ER.
Perspective: Abuse-deterrent drugs were intended to help fight opioid abuse. Yet, the persistence of the opioid epidemic indicates that vast improvements in abuse-deterrent technology are sorely needed. A new, high-viscosity, ER oxycodone formulation showed much improved abuse-deterrent properties in simulations of oral, injection, and inhalation abuse, compared to earlier, first-generation formulations.
References
Center for Disease Control and Prevention: Increases in drug and opioid overdose deaths—United States, 2000–2014. MMWR Morb Mortal Wkly Rep. 2015; 64: 1-5.
Ahmad F, Rossen L, Spencer M, et al.: Provisional Drug Overdose Death Counts. Hyattsville, MD: National Center for Health Statistics, 2018.
Substance Abuse and Mental Health Services Administration: Key Substance Use and Mental Health Indicators in the United States: Results from the 2016 National Survey on Drug Use and Health (HHS Publication No. SMA 17-5044, NSDUH Series H-52). Rockville, MD: Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration, 2017. Available at https://www.samhsa.gov/data/. Accessed August 23, 2018.
Center for Disease Control and Prevention: Wide-ranging online data for epidemiologic research (WONDER). 2016. Available at http://wonder.cdc.gov. Accessed August 23, 2018.
Compton W, Jones C, Baldwin G: Relationship between nonmedical prescription-opioid use and heroin use. N Engl J Med. 2016; 374: 154-163.
Adamchik Y, Frantseva MV, Weisspapir M, et al.: Methods to induce primary and secondary traumatic damage in organotypic hippocampal slice cultures. Brain Res Brain Res Protoc. 2000; 5: 153-158.
Lankenau S, Teti M, Silva K, et al.: Initiation into prescription opioid misuse amongst young injection drug users. Int J Drug Policy. 2012; 23: 37-44.
Pollini R, Banta-Green C, Cuevas-Mota J, et al.: Problematic use of prescription-type opioids prior to heroin use among young heroin injectors. Subst Abuse Rehabil. 2011; 2: 173-180.
Peavy K, Banta-Green C, Kingston S, et al.: “Hooked on” prescription-type opiates prior to using heroin: Results from a survey of syringe exchange clients. J Psychoactive Drugs. 2012; 44: 259-265.
Mateu-Gelabert P, Guarino H, Jessell L, et al.: Injection and sexual HIV/HCV risk behaviors associated with nonmedical use of prescription opioids among young adults in New York City. J Subst Abuse Treat. 2015; 48: 13-20.
National Institute on Drug Abuse: Prescription opioids and heroin. 2014. Available at https://www.drugabuse.gov/aboutnida/legislative-activities/testimony-to-congress/2014/prescription-opioid-heroin-abuse. Accessed August 23, 2018.
Cicero T, Ellis M: Abuse-deterrent formulations and the prescription opioid abuse epidemic in the United States: Lessons learned from OxyContin. JAMA Psychiatry. 2015; 72: 424-430.
US FDA: Guidance for industry: Abuse-deterrent opioids–Evaluation and labeling. 2015. Available at https://www.fda.gov/downloads/Drugs/Guidances/UCM334743.pdf. Accessed August 23, 2018.
Butler S, Black R, Fleming A: Relative abuse of crush-resistant prescription opioid tablets via alternative oral modes of administration. Pain Med. 2018; 19(8): 1613-1627.
Sellers E, Perrino P, Colucci S, et al.: Attractiveness of reformulated OxyContin® tablets: Assessing comparative preferences and tampering potential. J Psychopharmacol. 2013; 27: 808-818.
Friedmann N, Marsman M, deKater A, et al.: Reduced nasal abuse potential of REMOXY ER® versus commercially marketed oxycodone: A randomized clinical trial in recreational opioid users. J Opioid Manag. 2018; 14(6): 437-443.
Webster L, Bath B, Medve R: Opioid formulations in development designed to curtail abuse: Who is the target? Expert Opin Investig Drugs. 2009; 18: 255-263.
Webster L: Interpreting labels of abuse-deterrent opioid analgesics. J Opioid Manag. 2017; 13: 415-423.
Published
How to Cite
Issue
Section
License
Copyright 2005-2024, Weston Medical Publishing, LLC
All Rights Reserved
