title: Evaluation of the tamper-resistant properties of tapentadol extended-release tablets: results of in vitro laboratory analyses.
abstract: OBJECTIVE
  To evaluate tamper-resistant properties of tapentadol tablets formulated with polyethylene oxide (PEO) matrix.
  
  
  METHODS
  Analytical and physical tests to characterize tablets.
  
  
  METHODS
  Tapentadol extended release (ER) 50, 100, 150, 200, and 250 mg.
  
  
  METHODS
  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.
authors.affiliation: Pharmaceutical Development and Drug Delivery, Grünenthal GmbH, Aachen, Germany.
authors.forename: Eric
authors.initials: E
authors.lastname: Galia
authors.affiliation: Janssen Research & Development, LLC, Spring House, Pennsylvania.
authors.forename: Yinka
authors.initials: Y
authors.lastname: Williams
authors.affiliation: Janssen Research & Development, A Division of Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Ben
authors.initials: B
authors.lastname: Van Hove
authors.affiliation: Naples Anesthesia and Pain Associates and HAL Division, NEMA Research Inc, Naples, Florida.
authors.forename: Joseph
authors.initials: J
authors.lastname: Pergolizzi
authors.affiliation: Janssen Research & Development, LLC, Raritan, New Jersey.
authors.forename: Mila
authors.initials: M
authors.lastname: Etropolski
authors.affiliation: Janssen Scientific Affairs, LLC, Raritan, New Jersey.
authors.forename: Gary
authors.initials: G
authors.lastname: Vorsanger
mesh_terms: D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D010636:Phenols / Q000737:chemistry*; D012995:Solubility; D013607:Tablets; D000077432:Tapentadol
chemical_list: D003692:Delayed-Action Preparations; D010636:Phenols; D013607:Tablets; D000077432:Tapentadol