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Evaluation of the tamper-resistant properties of tapentadol extended-release tablets: Results of in vitro laboratory analyses

Eric Galia, PhD, Yinka Williams, PhD, Ben Van Hove, Joseph Pergolizzi, MD, Mila Etropolski, MD, Gary Vorsanger, PhD, MD



Objective: To evaluate tamper-resistant properties of tapentadol tablets formulated with polyethylene oxide (PEO) matrix.

Design: Analytical and physical tests to characterize tablets.

Interventions: Tapentadol extended release (ER) 50, 100, 150, 200, and 250 mg.

Main outcome measure(s): Mechanical resistance of tapentadol ER tablets to crushing (all doses), in vitro drug-release profiles of intact and tampered 50- and 250-mg tablets, and resistance to extraction of 250-mg tablets subjected to hammering.

Results: Crush resistance testing showed no deformation of tablets with two metal spoons, minimal deformation (no pulverization/breakage) with a pill crusher, slight deformation with a standardized pharmacopeia breaking force tester, and flattening (no pulverization/breakage) with a standardized hammer instrument. Mean in vitro release profiles in quality control medium (0.050 M phosphate buffer, pH 6.8) were similar with intact and tampered (pill crusher) tablets; the release profile was faster for hammered than intact tablets, with 30 percent of the drug released after 30 minutes (slightly higher than maximum release allowed per drug product specifications). Intact tablets were completely resistant to extraction in most organic solvents tested; in aqueous solvents, the amount of drug extracted increased with time. Hammered tablets were less resistant to extraction but required vigorous shaking over extended periods of time to release >50 percent of active ingredient.

Conclusions: In vitro results from tampering attempts presented herein demonstrate that tapentadol ER tablets were resistant to these forms of physical manipulation. Tapentadol ER tablets were also generally resistant to dissolution in most solvents. Developing tamper-resistant formulations is an important step in strategies to mitigate opioid abuse.



tamper-resistant formulation, oral opioid analgesic, tapentadol, opioid risk management

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Boudreau D, Von KM, Rutter CM, et al.: Trends in long-term opioid therapy for chronic non-cancer pain. Pharmacoepidemiol Drug Saf. 2009; 18 (12): 1166 - 1175.

Braden JB, Fan MY, Edlund MJ, et al.: Trends in use of opioids by noncancer pain type 2000-2005 among Arkansas Medicaid and healthcore enrollees: Results from the TROUP Study. J Pain. 2008; 9 (11): 1026 - 1035.

Volkow ND, Mclellan TA, Cotto JH, et al.: Characteristics of opioid prescriptions in 2009. JAMA. 2011; 305 (13): 1299 - 1301.

Katz NP, Adams EH, Benneyan JC, et al.: Foundations of opioid risk management. Clin J Pain. 2007; 23 (2): 103 - 118.

Okie S: A flood of opioids, a rising tide of deaths. N EnglJ Med. 2010; 363 (21): 1981 - 1985.

Rauck RL: What is the case for prescribing long-acting opioids over short-acting opioids for patients with chronic pain?. A critical review. Pain Pract. 2009; 9 (6): 468 - 479.

Butler SF, Black RA, Cassidy TA, et al.: Abuse risks and routes of administration of different prescription opioid compounds and formulations. Harm Reduct J. 2011; 8: 29.

Rubino D: Experience with an extended-release opioid formulation designed to reduce abuse liability in a community-based pain management clinic. Int J Gen Med. 2011; 4: 617 - 626.

US Department of Health and Human Services, Food And Drug Administration, Center For Drug Evaluation And Research, et al.: Guidance for Industry. Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment. Available at Accessed March 25, 2013.

H.R. 486 (113th): Stop Tampering of Prescription Pills Act of 2013. Available at Accessed August 2, 2013.

Centers for Disease Control and Prevention: Press Release: Opioids Drive Continued Increase in Drug Overdose Deaths. Available at Accessed March 25, 2013.

Statement by Leonard J. Paulozzi. Trends in Unintentional Drug Overdose Deaths. Before the Judiciary Committee, Subcommittee on Crime and Drugs, U.S. Senate. Available at Accessed August 2, 2013.

Tzschentke TM, Jahnel U, Kogel B, et al.: Tapentadol hydrochloride: A next-generation, centrally acting analgesic with two mechanisms of action in a single molecule. Drugs Today (Barc). 2009; 45(7): 483 - 496.

Dart RC, Cicero TJ, Surratt HL, et al.: Assessment of the Abuse of Tapentadol Immediate Release: The First 24 Months. J Opioid Manag. 2012; 8(6): 395 - 402.

Cepeda MS, Fife D, Vo L, et al.: Comparison of opioid doctor shopping for tapentadol and oxycodone: A cohort study. J Pain. 2013; 14(2): 158 - 164.

Bartholomaeus JH, Arkenau-Maric E, Galia E: Opioid extended-release tablets with improved tamper-resistant properties. Expert Opin Drug Deliv. 2012; 9(8): 879 - 891.

Proeschel PA, Morneburg T: Task-dependence of activity/bite-force relations and its impact on estimation of chewing force from EMG. J Dent Res. 2002; 81(7): 464 - 468.

Vosburg SK, Jones JD, Manubay JM, et al.: A comparison among tapentadol tamper-resistant formulations (TRF) and OxyContin® (non-TRF) in prescription opioid abusers. Addiction. 2013; 108(6): 1095 - 1096.

Fishman SM: Recognizing pain management as a human right: A first step. Anesth Analg. 2007; 105(1): 8 - 9.

Johannes CB, Le TK, Zhou X, et al.: The prevalence of chronic pain in United States adults: Results of an Internet-based survey. J Pain. 2010; 11(11): 1230 - 1239.

Chronic Pain in America: Roadblocks to Relief. A Study Conducted by Roper Starch Worldwide for American Academy of Pain Medicine, American Pain Society and Janssen Pharmaceutica, 1999. Available at Accessed February 21, 2007.

Brennan F, Carr DB, Cousins M: Pain management: A fundamental human right. Anesth Analg. 2007; 105(1): 205 - 221.

Pergolizzi J: Musculoskeletal pain: Current and Future Management Strategies. Presented at the 5th Association of South-East Asian Pain Societies (ASEAPS) Conference, May 2-5, 2013, Singapore, 2013.

US Food and Drug Administration: FDA Approves Abuse-Deterrent Labeling for Reformulated OxyContin. Press Release Dated April 16, 2013. Available at Accessed August 2, 2013.

Dart RC, Bartelson BB, Adams EH: Non-medical use of tapentadol immediate release by college students. Clin J Pain. 2014 (in press).


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