The effects of tampering on the rate-controlling mechanism of Remoxy®, an extended-release oxycodone

Abstract

Remoxy® (King Pharmaceuticals, Inc., Bristol, TN) is a water-insoluble, highly-viscous, oral formulation of extended-release oxycodone currently in development and designed to maintain its rate-controlling characteristics following common forms of physical manipulation or chemical challenge. Three single-center, phase I, in vivo studies were conducted in healthy volunteers to investigate attempts to defeat these characteristics and the resulting effects on the pharmacokinetic profile of Remoxy. Studies A and B assessed the effect of buccal dissolution and chewing, respectively, on Remoxy 40-mg capsules (fed) compared with oral Remoxy whole (fed) and oxycodone immediate release (IR) solution (40 mg; fasted). Study C compared the pharmacokinetics of Remoxy 40-mg capsules whole or crushed/co-ingested with 40% ethanol with that of OxyContin 40 mg (Purdue Pharma LP, Stamford, CT) whole or crushed/co-ingested with 40% ethanol and oxycodone IR solution (40 mg). Although buccal dissolution, chewing, and crushing followed by co-ingestion with 40% ethanol resulted in an increase in the rate of absorption of oxycodone from Remoxy, this increase was not consistent with dose dumping. This was demonstrated in all studies by the lower Cmax and partial AUCs of Remoxy compared with the oxycodone IR solution as well as a significantly longer Tmax associated with Remoxy. Attempts to defeat the rate-controlling characteristics of Remoxy by chewing, crushing and extraction with ethanol, or by buccal administration were not successful as they did not lead to rapid release and absorption of oxycodone (ie, dose-dumping), thereby demonstrating that Remoxy performed as designed. Pain Therapeutics, Inc. funded this study.