Presented at the 2013 AAPM Annual Meeting « Back

Tamper-Resistant Properties of Tapentadol Extended-Release Tablets

Joseph Pergolizzi, MD, jpjmd@msn.com¹, Eric Galia², Yinka Williams, PhD³, Ben Van Hove4, Mila Etropolski³, (1) Johns Hopkins University SOM, Naples, Florida, (2) Grunenthal GmbH, Aachen, North Rhine Westfalia, Germany, (3) Amercian Association of Pharmaceutical Scientists, Spring House, Pennsylvania, (4) Janssen Pharmaceuticals, Beerse, Antwerp, Belgium

Purpose: We evaluated the tamper-resistant properties of tapentadol tablets (NUCYNTA® ER, Janssen Pharmaceuticals, Inc.), consisting of a polyethylene oxide (PEO) matrix. Methods: For all dose strengths (50, 100, 150, 200, 250 mg), crushing tests were performed with spoons, a pill crusher, a breaking force tester, and a hammer. Frozen 250 mg tablets (-20°C) were tested with the breaking force tester. We tested for dissolution in 40% ethanol and extraction in 10 solvents (isopropanol, acetone, ethyl acetate, 40% ethanol, absolute ethanol, methanol, water, 0.1N HCl, 0.1N NaOH, and organic food corn oil). Results: Tapentadol PEO tablets showed minimal to no deformation by spoons, the pill crusher, and breaking force tester (>1,000 N); hammered tablets flattened but did not break. The mean in vitro release profile in QC medium was similar to controls. Intact tablets showed a slower release in 40% ethanol. Tablets resisted extraction at one hour in acetone, ethanol, ethyl acetate, isopropanol, and oil. In one hour, the mean amount of extracted drug reached a maximum of 20% in 0.1N HCl, 0.1N NaOH, 40% ethanol, and water; 32% in methanol. From hammered tablets, ≤11% in acetone, ethyl acetate, isopropanol, and oil; ≤6 2% in in 0.1N HCl, 0.1N NaOH, 40% ethanol, absolute ethanol, and water; 86% in methanol could be extracted. Conclusions: Tapentadol PEO tablets resisted crushing and extraction in five solvents. Solvents that partially extracted tapentadol PEO (methanol, 0.1N HCl, 0.1N NaOH, 40% ethanol, and water) would require additional steps to obtain pure drug.

Funding: Pharmaceutical Development and Drug Delivery, Grünenthal GmbH, Aachen, Germany and Janssen Research & Development, L.L.C., Spring House, Pennsylvania