TY - JOUR
T1 - Evaluation of the tamper-resistant properties of tapentadol extended-release tablets
T2 - Results of in vitro laboratory analyses
AU - Galia, Eric
AU - Williams, Yinka
AU - Van Hove, Ben
AU - Pergolizzi, Joseph
AU - Etropolski, Mila
AU - Vorsanger, Gary
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Opioid risk management
KW - Oral opioid analgesic
KW - Tamper-resistant formulation
KW - Tapentadol
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U2 - 10.5055/jom.2014.0203
DO - 10.5055/jom.2014.0203
M3 - Article
C2 - 24944065
AN - SCOPUS:84904501417
VL - 10
SP - 149
EP - 158
JO - Journal of Opioid Management
JF - Journal of Opioid Management
SN - 1551-7489
IS - 3
ER -