Polyethylene Oxide Tapentadol ER Formulation Proves Crush-Resistant

LAS VEGAS, NV — At PAINWeek 2012, study data showed that tapentadol extended-release (ER) tablets formulated with a polyethylene oxide matrix produced tablets that were resistant to crushing or extraction, as reported by Joseph Pergolizzi, MD, of Naples Anesthesia and Pain Associates, Naples, FL.

Tapentadol, a centrally acting analgesic, is available in an extended-release formulation for the management of moderate-to-severe chronic pain in adults when a continuous, around-the-clock opioid analgesic is needed for an extended period of time. These tablets are formulated with a polyethylene oxide matrix using a melt extrusion manufacturing process to produce high mechanical strength tablets that are resistant to crushing or extraction (INTAC tamper-resistant technology, Grünenthal, Aachen, Germany).

Dr. Pergolizzi and colleagues conducted a battery of analytical and physical characterization tests to evaluate the tamper-resistant properties of polyethylene oxide-based tapentadol tablets. An attempt to crush each dosage strength (50mg, 100mg, 150mg, 200mg, and 250mg) was made using four different tools: two commercially available metal spoons, an Ocelco Inc. professional metal pill crusher, a standardized pharmacopeia breaking force tester (USP 1217), and a standardized hammer instrument (a 5kg steel weight was dropped once onto the tablet from an 80cm height, with impact energy force=39.2Nm).

A quality control dissolution method (performed in 900mL of 0.050M phosphate buffer pH 6.8) was used to evaluate the in vitro drug release profiles of control tapentadol polyethylene oxide tablets and those subjected to the pill crusher and the hammer instrument. In addition, the resistance to extraction of control 250mg tapentadol polyethylene oxide tablets and those subjected to tampering by hammering were evaluated by shaking these tablets vigorously for 15 minutes and 1 hour in 10 different solutions (isopropanol, acetone, ethyl acetate, 40% ethanol, absolute ethanol, methanol, water, 0.1N HCl, 0.1N NaOH, and organic food corn oil).

Study results showed no deformation of the tapentadol polyethylene oxide tablets was possible when using two spoons to crush the tablets. With the pill crusher, only minimal deformation (no breakage/pulverization) was observed for all dosage strengths. Using the breaking force tester, all tapentadol tablets were resistant to crushing (breaking fore >1,000N) and tablets were only visibly deformed; likewise, frozen tablets were resistant to crushing and only deformed to a similar degree as unfrozen tablets. With the hammer, the tablet was flattened but not pulverized or broken into pieces.  The mean in vitro release profile in standard quality control medium was similar to control tablets for those tampered by the pill crusher, and was somewhat faster for the hammered tablets. The mean in vitro release profile of control tapentadol was slower in the 40% ethanol solution than in quality control medium, which indicates no dose dumping in either medium.

Dr. Pergolizzi concluded that tapentadol polyethylene oxide tablets were strongly resistant to crushing using the spoons, pill crusher, and breaking force tester. They were flattened with the hammer, which indicates mechanical resistance to tampering. Furthermore, in vitro dissolution testing showed that this formulation not only resists tampering but also prevents immediate release of active ingredient.