Controlled Release Dosage Form of Narcotic Antagonist(II) : Biocompatibility and Pharmacokinetics of Naloxone Implant

For the effective administration of narcotic antagonist, the application of sustained release implantable systems with biodegradable polyphosphazene was examined. Using poly[(diethyl glutamate)-co-(ethyl glycinate) phosphazene], the implantable devices containing naloxone hydrochloride were prepared and in vivo implantation studies were carried out subcutaneously in rat and rabbit with this preparation for the biocompatibility and pharmacokinetics. The histological finding in rats at initial time period was the inflammation that occurred focally around the implants, but they were showed subsequent mild and limited chronic inflammations and the irreversible changes such as necrosis and degeneration of the muscle or connective tissues were not observed. Therefore the placebo and naloxone implants are considered to be biocompatible formulations histologically. In pharmacokinetic studies, the release of naloxone from the naloxone implants into blood plasma was maintained in 192 hours, but the initial burst effect was observed. If this problem was solved, the application for the narcotic antagonist sustained release systems can be expected.