Misuse resistant formulations for controlled release opioid drugs

摘要

Controlled release formulations, especially those designed for once-daily administration contain amounts of drug that could be harmful if released as a bolus - so called dose dumping; such considerations are especially important for controlled release opioid drugs as these may cause severe side-effects if high plasma concentrations are reached quickly. Tramadol hydrochloride (tramadol) is a mixed mechanism opioid that, while unassociated with the abuse that occurs with stronger opioids, nevertheless warrants a robust controlled release formulation if dose dumping is not to occur through accidental misuse. Here we describe the performance of a new misuse-resistant (MR) formulation of tramadol that in vivo displayed a plasma profile consistent with early onset and sustained analgesia. The formulation is scored, to allow breaking, but very hard to avoid crushing. Bisected tablets display 20hr controlled release in vitro and, should crushing be achieved, the resultant powder exposed to aqueous solution forms a hard gel that prevents extraction and retains controlled release properties independent of pH or alcohol. The properties displayed by these MR tablets may reduce the likelihood of serious adverse events occurring should accidental misuse of the medication take place.