Bridging from conventional marketed immediate release formulations to new tamper resistant alternatives

Many solid immediate release (IR) dosage forms containing opioids can be abused by snorting of crushed product or preparation of solutions for subsequent injection. Tamper resistant IR formulations (TRF-IR) aim to prevent intentional abuse by crushing and dissolving. Gruenenthal (GRT) has developed a TRF technology (INTAC®) for extended release formulations, already available as marketed products. The technology has now been expanded for IR formulations using also a high molecular weight polymer as excipient. A switch from a conventional immediate release formulation to TRF product alternatives generally requires bridging bioequivalence studies. A GRT-TRF IR formulation (Test) was investigated in an open, randomized, cross-over, relative bioavailability trial against the reference marketed IR formulation of an analgesic product. Single oral doses were administered to healthy male subjects under fasted conditions. Serum drug concentrations were determined by a validated LC-MS/MS method. Non-compartmental PK analysis was performed and the usual 80.00-125.00% confidence interval acceptance criteria for bioequivalence were used for comparing Test to the reference. The 90% confidence intervals for Cmax and AUC0-t of Test were 89.74 - 117.32% and 94.24-109.97%, respectively. The data demonstrate that GRT-TRF-IR tablets have comparable in-vivo performance to standard immediate release formulations. TRF-IR tablets may enable physicians to simply switch patients from conventional to reformulated TRF products. The study was sponsored by Gruenenthal GmbH.