Biocompatibility studies of naltrexone sustained release formulations

In vivo implantation studies were carried out subcutaneously in rats and rabbits with naltrexone sustained release preparations which included placebo beads, naltrexone containing beads, and naltrexone microspheres. Naltrexone plasma concentrations in rats and rabbits, and the histopathological tissue reactions utilizing standard procedures and light microscopic evaluation to the respective naltrexone preparations were determined at days 3, 7, 14, 21 and 28. The total drug doses in rat and rabbit plasmas, respectively, vs. implantation times were also calculated. The only significant histological finding in both rats and rabbits at any time period was the inflammation that occurred focally around the beads or microspheres. The focal inflammatory cell density in both rats and rabbits was higher for the naltrexone beads than for the placebo beads at days 14, 21 and 28 respectively. This difference in inflammatory response between naltrexone beads and placebo beads increased with increasing time of implantation. Considering the resolution of the inflammatory response for the placebo beads with implantation time in both rats and rabbits, it is suggested that the naltrexone drug itself is the causative agent of the focal inflammation present surrounding the naltrexone beads in the implant sites.